[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-renal-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-renal-cell-carcinoma":28},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,27,0,25,[9,46,78,100,214,245,276,313,340,362,384,408,438,473,493,516,543,609,630,652,677,701,732,761,787],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":30,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100580336","phase-1-a-study-of-abemaciclib-and-cabozantinib-in-people-with-clear-cell-renal-cell-carcinoma-ccrcc-100580336",false,"NCT06835972","A Study of Abemaciclib and Cabozantinib in People With Clear Cell Renal Cell Carcinoma (ccRCC)","A Phase 1b\u002F2 Study of Abemaciclib Plus Cabozantinib in Immune Checkpoint Blockade-pretreated Metastatic Clear Cell Renal Cell Carcinoma","Inclusion Criteria:\n\n* Age ≥ 18 years at the time of informed consent\n* Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot\n* Signed and dated IRB-approved Informed Consent Form\n* Patient must have a histologically confirmed diagnosis of metastatic stage IV clear cell renal cell carcinoma or metastatic stage IV translocation-associated renal cell carcinoma.\n* Patient should have availability of archival tissue that enables definitive diagnosis of ccRCC or tRCC, per review at participating site, accompanied by an associated pathology report. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion. NOTE: If archival tissue is unavailable, a patient can still enroll onto the study with documented confirmation from the study PI.\n* Patients must have at least one extra-skeletal, extracranial measurable lesion as defined by RECIST v1.1\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2\n* Patients must have received prior therapy with at least 2 approved systemic agents and a maximum of 3 prior lines of systemic therapy. Prior adjuvant therapy is permitted.\n* Patient must have progressed on 1 prior PD-1 or PD-L1 targeted treatment and prior VEGFR directed TKI therapy\n* Patients must have recovered to baseline or \\\u003C Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events (AEs) are clinically non-significant and\u002For stable on supportive therapy (See Appendix 2)\n* Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.\n* The patient can swallow oral medications.\n* Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:\n* ANC ≥ 1500 cells\u002FμL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)\n* WBC counts ≥ 2500\u002FμL and ≤ 15,000\u002FμL without G-CSF\n* Absolute Lymphocyte count \\> 0.5K\u002FmcL\n* Platelet count ≥100,000\u002FμL (without transfusion within 2 weeks prior to Cycle 1, Day 1)\n* Hemoglobin ≥9.0 g\u002FdL (without transfusion within 2 weeks prior to Cycle 1, Day 1)\n* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 X upper limit of normal (ULN). ALP ≤ 5 x ULN if patient has documented bone metastases.\n* Serum bilirubin ≤ 1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 2 x ULN may be enrolled.\n* Serum albumin ≥ 2.8 g\u002Fdl\n* (PT)\u002FINR or partial thromboplastin time (PTT) test \\\u003C 1.3x the laboratory ULN\n* Estimated Glomerular Filtration Rate (eGFR) ≥ 30mL\u002Fmin using the CKD-EPI formula https:\u002F\u002Fwww.kidney.org\u002Fprofessionals\u002Fkdoqi\u002Fgfr\\_calculator.\n* Urine protein\u002Fcreatinine ratio (UPCR) ≤ 1.8 mg\u002Fmg\n* Women of childbearing potential must not be pregnant or lactating at screening.\n* Women of childbearing potential who are sexually active with a non-sterilized male partner must use two methods of effective contraception from screening and must agree to continue using such precautions for 4 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.\n* Sexually active participants must agree to use medically accepted methods of contraception (i.e. barrier methods including condoms, female condom, or diaphragm with spermicidal gel) during the study and for 4 months after the last dose of the study treatment. Male patients must agree not to donate sperm during the study treatment period and for 4 months after the last dose Female patients must agree not to donate eggs during the study period and for 4 months after the last dose.\n\nExclusion Criteria:\n\n* Prior treatment with abemaciclib or cabozantinib.\n* Receipt of any type of anti-cancer antibody, cytotoxic anticancer therapy, or any other investigational agents within 2 weeks of treatment start or 5 half-lives, whichever is shorter. For immune checkpoint inhibitors, patients must have discontinued treatment 28 days prior to trial enrollment.\n* Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they are neurologically stable for 4 weeks, have completed radiation therapy or surgery, and recovered from side effects. Patients must have discontinued steroid therapy for at least 2 weeks prior to first dose of study treatment.\n* Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or early stage cancers previously treated with curative intent.\n* Patients requiring moderate or strong CYP3A4 inducers or inhibitors (https:\u002F\u002Fdruginteractions.medicine.iu.edu\u002FMainTable.aspx).\n* Patients with a history of HIV infection who are not on a stable HAART regimen and\u002For are requiring antimicrobials for prevention of opportunistic infections and\u002For have CD4 count below 250 or a detectable HIV viral load\n* Patients with active hepatitis B or hepatitis C infection with detectable viral load by PCR\n* Active systemic bacterial infection (requiring systemic antibiotics at time of initiating study treatment) or fungal infection.\n* History of significant cardiovascular events or active cardiovascular disease; including myocardial infarction within the previous 6 months, unstable arrhythmias, unstable angina, prior sudden cardiac arrest, LVEF \\\u003C 50% by echocardiogram (ECHO).\n* Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 150 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n* Significant arterial disease (e.g., stroke, transient ischemic attack, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.\n* Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 470 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.\n\nNote: If a single ECG shows a QTcF with an absolute value \\> 470 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility\n\n* Concomitant anticoagulation with coumadin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n\n  * Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n  * Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.\n* Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).\n* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)\n* Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 6 weeks before first dose of study treatment. Completeness of wound healing from any surgery must be ascertained. There must be a minimum of two weeks from completion of wound healing to start of study.\n* Evidence of tumor invading the gastrointestinal tract, active peptic ulcer disease, active inflammatory bowel disease, active diverticulitis, active cholecystitis, symptomatic\u002Factive cholangitis or appendicitis, acute pancreatitis, acute obstruction of pancreatic duct or common bile duct, or active gastric outlet obstruction.\n* Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.\n* Patients with a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment.\n* The patient has tumor invading or encasing any major blood vessels, with exception of renal vessels ipsilateral to the primary renal tumor.\n* The patient has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus) at time of study screening.\n* Patients with malabsorption syndrome.\n* Patients with a serious non-healing wound\u002Fulcer\u002Fbone fracture.\n* Patients with active COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to first dose of study treatment.\n* Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n* Radiation therapy for bone metastasis within 2 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n* The patient has serious and\u002For uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).","ALL","18 Years",{"count":20,"type":21},43,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","The researchers are doing this study to find out whether the combination of abemaciclib and cabozantinib is a safe and effective treatment for people with metastatic clear cell renal cell carcinoma (ccRCC) and translocation-associated renal cell cancer (tRCC). The researchers will test different doses of the study drugs to find the highest doses that cause few or mild side effects in participants.",[28,29],"Metastatic Renal Cell Carcinoma","Translocation Renal Cell Carcinoma",[31,32],"Abemaciclib","Cabozantinib","RECRUITING","2026-06-23",{"date":36,"type":37},"2026-06-24","ACTUAL",{"date":39,"type":37},"2025-02-14",{"date":41,"type":21},"2027-02",{"name":43,"class":44},"Memorial Sloan Kettering Cancer Center","OTHER",8,{"id":47,"slug":48,"hasResults":12,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":4,"eligibilityCriteria":52,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":22,"phases":55,"briefSummary":57,"conditions":58,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":71,"completionDateStruct":73,"leadSponsor":75,"locationsCount":77},"100554543","phase-3-testing-longer-duration-radiation-therapy-versus-the-usual-radiation-therapy-in-patients-with-cancer-that-has-spread-to-the-brain-100554543","NCT06500455","Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain","Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases","Inclusion Criteria:\n\n* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:\n\n  * Non-small cell lung cancer\n  * Melanoma\n  * Breast cancer\n  * Renal cell carcinoma\n  * Gastrointestinal cancer\n  * If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest\u002Fabdomen\u002Fpelvis, positron emission tomography \\[PET\\]\u002FCT, etc.) is required\n* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration\n* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm\n* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension\n\n  * Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS\u002FFSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator\n* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5\n* No more than 2 lesions planned for resection if clinically indicated\n* No known leptomeningeal disease (LMD)\n\n  * Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and\u002For unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion\n* Age ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 60\n* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \\[PCI\\])\n* New York Heart Association Functional Classification II or better (NYHA Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects\n* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy",{"count":54,"type":21},269,[56],"PHASE3","This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.",[59,60,61,62,63,64,65,28,66,67],"Anatomic Stage IV Breast Cancer AJCC v8","Metastatic Breast Carcinoma","Metastatic Digestive System Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Neoplasm in the Brain","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","2026-06-22",{"date":70,"type":37},"2026-06-25",{"date":72,"type":37},"2024-12-12",{"date":74,"type":21},"2028-06-30",{"name":76,"class":44},"NRG Oncology",270,{"id":79,"slug":80,"hasResults":12,"nctId":81,"briefTitle":82,"officialTitle":83,"acronym":84,"eligibilityCriteria":85,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":86,"targetDuration":4,"studyType":22,"phases":88,"briefSummary":89,"conditions":90,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":93,"startDateStruct":94,"completionDateStruct":96,"leadSponsor":98,"locationsCount":99},"100464437","phase-2-testing-the-addition-of-stereotactic-radiation-therapy-with-immune-therapy-for-the-treatment-of-patients-with-unresectable-or-metastatic-renal-cell-cancer-samurai-trial-100464437","NCT05327686","Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial","Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)","SAMURAI","Inclusion Criteria:\n\n* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration\n* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:\n\n  * History\u002Fphysical examination within 45 days prior to registration\n  * CT\u002Fmagnetic resonance imaging (MRI) of the chest\u002Fabdomen\u002Fpelvis within 45 days prior to registration\n* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\\>= 3 factors)\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor\n* Patient not recommended for or refused immediate cytoreductive nephrectomy\n* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen\n* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging\n* Age \\>= 18\n* Karnofsky performance status \\>= 60 within 45 days prior to registration\n* Hemoglobin \\>= 8 g\u002FdL (transfusions are allowed) (within 45 days prior to registration)\n* Platelet count \\>= 50,000\u002Fmm\\^3 (within 45 days prior to registration)\n* Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 (within 45 days prior to registration)\n* Calculated (Calc.) creatinine clearance \\>= 30 mL\u002Fmin (within 45 days prior to registration)\n\n  * Creatinine clearance (CrCl) \\>= 30 mL\u002Fmin estimated by Cockcroft-Gault Equation\n  * For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \\>= 30 mL\u002Fmin\u002F1.73m\\^2 will be considered adequate\n* Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \\\u003C 3.0 mg\u002FdL) (within 45 days prior to registration)\n* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\\\u003C 3 x upper limit of normal (ULN) or \\\u003C 5 x ULN if hepatic metastases present (within 45 days prior to registration)\n* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load\n* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information\n\nExclusion Criteria:\n\n* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment\n* Patients with untreated or unstable brain metastases or cranial epidural disease\n\n  * Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator\n* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor\n* Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \\> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \\> 3 years prior to registration)\n* Severe, active comorbidity defined as follows:\n\n  * Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease\n  * History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies\n  * Active tuberculosis (purified protein derivative \\[PPD\\] response without active tuberculosis \\[TB\\] is allowed)\n  * Uncontrolled hypertension (systolic blood pressure \\[BP\\] \\>= 190 mmHg or diastolic BP \\> 110 mmHg)\n  * Major surgery requiring hospital admission =\\\u003C 28 days prior to registration\n  * Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration\n  * Any arterial thrombotic (ST elevation myocardial infarction \\[STEMI\\], non-ST elevation myocardial infarction \\[NSTEMI\\], cerebrovascular accident \\[CVA\\], etc) events within 180 days prior to registration\n  * Active New York (NY) Heart Association class 3-4 heart failure symptoms\n  * Moderate or severe hepatic impairment (Child-Pugh B or C)\n  * Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \\> 30 days prior to registration is allowed)\n  * Unstable cardiac arrhythmia within 180 days prior to registration\n  * History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration\n  * History of or active inflammatory bowel disease\n  * Malabsorption syndrome within 45 days prior to registration\n* Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\\\u003C 45 days prior to registration",{"count":87,"type":21},240,[25],"This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.",[28,91,67,92],"Stage III Renal Cell Cancer AJCC v8","Unresectable Renal Cell Carcinoma",{"date":70,"type":37},{"date":95,"type":37},"2023-02-01",{"date":97,"type":21},"2028-06-15",{"name":76,"class":44},328,{"id":101,"slug":102,"hasResults":12,"nctId":103,"briefTitle":104,"officialTitle":105,"acronym":106,"eligibilityCriteria":107,"healthyVolunteers":12,"sex":17,"minAge":108,"maxAge":4,"enrollmentInfo":109,"targetDuration":4,"studyType":22,"phases":111,"briefSummary":112,"conditions":113,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":205,"lastUpdatePostDateStruct":206,"startDateStruct":207,"completionDateStruct":209,"leadSponsor":211,"locationsCount":213},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":110,"type":21},132,[24,25],"This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[114,115,116,117,59,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,62,64,65,155,28,156,157,158,159,160,161,162,91,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,66,67,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,92,197,198,199,200,201,202,203,204],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Merkel Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","2026-06-18",{"date":34,"type":37},{"date":208,"type":37},"2022-03-31",{"date":210,"type":21},"2028-03-31",{"name":212,"class":44},"Mayo Clinic",1,{"id":215,"slug":216,"hasResults":12,"nctId":217,"briefTitle":218,"officialTitle":219,"acronym":4,"eligibilityCriteria":220,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":221,"targetDuration":4,"studyType":22,"phases":223,"briefSummary":225,"conditions":226,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":236,"lastUpdatePostDateStruct":237,"startDateStruct":239,"completionDateStruct":241,"leadSponsor":243,"locationsCount":213},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":222,"type":21},160,[224],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[227,228,229,230,231,232,233,234,153,154,62,64,65,28,235,161,162,91,177,66,67],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":238,"type":37},"2026-06-12",{"date":240,"type":37},"2026-06-08",{"date":242,"type":21},"2028-12-31",{"name":244,"class":44},"OHSU Knight Cancer Institute",{"id":246,"slug":247,"hasResults":12,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":251,"eligibilityCriteria":252,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":253,"targetDuration":4,"studyType":22,"phases":255,"briefSummary":256,"conditions":257,"keywords":260,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":266,"lastUpdatePostDateStruct":267,"startDateStruct":269,"completionDateStruct":271,"leadSponsor":273,"locationsCount":275},"100595105","phase-4-digital-monitoring-of-self-reported-symptoms-by-patients-treated-with-cabozantinib-plus-nivolumab-for-advanced-clear-cell-renal-carcinoma-100595105","NCT07028125","Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma","Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma: The CANIQOL Multicentre Study","CANIQOL","Inclusion Criteria:\n\n* Patient older than 18 years\n* Diagnosis of advanced\u002Fmetastatic Renal Cell Carcinoma (RCC) with a clear-cell component\n* No prior systemic treatment for RCC\n* Physician-initiated decision prior to study enrollment to treat with cabozantinib and nivolumab in combination, in first line for advanced\u002Fmetastatic RCC, according to approved local labels\n* Female subjects of childbearing potential must not be pregnant at screening and during treatment by Cabozantinib and Nivolumab. Effective methods of contraception must be used throughout the course of treatment and for at least 5 months after the end of treatment. Sexually active fertile subjects and their partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the study and 5 months after the last dose of study treatment, even if oral contraceptives are also used.\n* Subject affiliated to an appropriate social security system\n* Patient has signed informed consents obtained before any trial related activities and according to local guidelines\n\nExclusion Criteria:\n\n* Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol\n* Current participation in another clinical study and\u002For in an investigational program with any intervention that could possibly interfere with the treatment and impact this study\n* Patient with history of allergy or hypersensitivity to components of the study drugs\n* Patient with contraindication to the study drugs\n* Pregnant or lactating woman\n* Patient unable to use digital tools\n* Patient deprived of liberty or placed under the authority of a tutor\n* Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol",{"count":254,"type":21},83,[224],"The aim of the study is to evaluate the impact of digital monitoring of self-reported symptoms (PROs) on the adjustment of treatment management in patients treated with cabozantinib plus nivolumab for advanced clear cell renal cell carcinoma (RCC) in real life during the first 3 months of combined treatment",[258,28,259],"Renal Cell Carcinoma (Kidney Cancer)","Locally Advanced",[261,262,263,264,265],"kidney cancer","metastatic","cabozantinib","nivolumab","digital monitoring system","2026-06-04",{"date":268,"type":37},"2026-06-05",{"date":270,"type":37},"2025-10-01",{"date":272,"type":21},"2029-01",{"name":274,"class":44},"Centre Francois Baclesse",16,{"id":277,"slug":278,"hasResults":12,"nctId":279,"briefTitle":280,"officialTitle":281,"acronym":4,"eligibilityCriteria":282,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":283,"targetDuration":4,"studyType":22,"phases":285,"briefSummary":286,"conditions":287,"keywords":299,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":303,"lastUpdatePostDateStruct":304,"startDateStruct":305,"completionDateStruct":307,"leadSponsor":309,"locationsCount":312},"100610425","phase-1-symbiotic-gu-08-a-study-to-learn-about-the-medicine-called-pf-08634404-dosed-alone-and-in-combination-with-other-anticancer-therapies-in-adults-with-locally-advanced-or-metastatic-renal-cell-cancer-100610425","NCT07227415","Symbiotic-GU-08: A Study to Learn About the Medicine Called PF-08634404 Dosed Alone and in Combination With Other Anticancer Therapies in Adults With Locally Advanced or Metastatic Renal Cell Cancer","AN INTERVENTIONAL PHASE 1B\u002F2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-08634404 MONOTHERAPY AND IN COMBINATION WITH OTHER ANTICANCER AGENTS IN ADULT PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC RENAL CELL CARCINOMA","Inclusion Criteria:\n\n* 18 years of age or older at screening\n* Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC with diagnosis confirmed by histology\u002Fcytology\n* At least one measurable (as defined by the investigator) and untreated lesion\n* Adequate hematologic, hepatic, cardiac and renal function\n* No prior systemic therapy for RCC (immunotherapy after surgery is allowed if received \\>12 months prior)\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n* All International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) based risk categories\n\nExclusion Criteria:\n\nParticipants may be excluded if they meet any of the following:\n\n* Known active brain lesions including leptomeningeal metastasis, brainstem, meningeal or spinal cord metastases or compression.\n* Clinically significant risk of haemorrhage or fistula\n* History of another malignancy within 3 years\n* History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n* active autoimmune diseases requiring systemic treatment within the past 2 years\n* uncontrolled cardiac and other comorbidities within 6 months prior to the first dose\n* Major surgery or severe trauma within 4 weeks before the first dose, or planned major surgery during the study\n* History of severe bleeding tendency or coagulation dysfunction\n* History of oesophageal varices, severe ulcers, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months prior to the first dose\n* Acute, chronic or symptomatic infections\n* Participants with history of immunodeficiency",{"count":284,"type":21},224,[24,25],"This study is testing a new medicine called PF-08634404 and how it works in adults with advanced Renal Cell Carcinoma (RCC)- a type of kidney cancer that is either locally advanced (spread to nearby tissues) or metastatic (spread to other parts of the body). The study will look at the safety of the study medicine, when given alone or with other anticancer medicines, and how this type of cancer responds to them.\n\nTo join the study, participants must be adults; with locally advanced or metastatic RCC; who have not received treatment for their advanced kidney cancer.\n\nParticipants will receive study medicine either alone or with other anticancer medicines. The medicine will be given through intravenous (IV) infusions, which means it will be injected directly into a vein. All treatments will take place at clinical study sites, where trained medical staff will take care of participants during and after each visit.",[288,233,289,290,291,28,292,293,294,295,296,297,298],"Carcinoma, Renal Cell","Renal Cancer","Renal Neoplasm","Clear Cell Renal Cell Carcinoma","Clear-cell Metastatic Renal Cell Carcinoma","Carcinoma, Renal Cell Metastasis","Advanced or Metastatic Renal Cell Carcinoma","Carcinoma, Renal Cell, Advanced","Metastatic Renal Cell Cancer","Metastatic Renal Cell Carcinoma ( mRCC)","Metastatic\u002FAdvanced Renal Cell Carcinoma",[300,301,302],"Renal cell carcinoma","renal cancer","renal neoplasm","2026-06-03",{"date":266,"type":37},{"date":306,"type":37},"2026-02-10",{"date":308,"type":21},"2028-11-01",{"name":310,"class":311},"Pfizer","INDUSTRY",109,{"id":314,"slug":315,"hasResults":12,"nctId":316,"briefTitle":317,"officialTitle":317,"acronym":4,"eligibilityCriteria":318,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":319,"enrollmentInfo":320,"targetDuration":4,"studyType":22,"phases":322,"briefSummary":323,"conditions":324,"keywords":327,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":330,"lastUpdatePostDateStruct":331,"startDateStruct":333,"completionDateStruct":335,"leadSponsor":337,"locationsCount":213},"100451171","phase-2-phase-ii-trial-of-combination-anti-pd-1-and-aldesleukin-for-metastatic-melanoma-and-renal-cell-carcinoma-100451171","NCT05155033","Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma","* INCLUSION CRITERIA:\n* Participants must have histologically or cytologically confirmed cancer that falls into one of three cohorts: (1) metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy; (2) metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1\u002FPDL1 based therapy; (3) metastatic or advanced locoregional melanoma not amenable to curative surgical resection and naive to anti-PD-1 therapy.\n* Participants must have measurable disease (per RECIST v1.1 criteria), metastatic melanoma or renal cell cancer.\n* Age \\>=18 years of age.\n* Clinical performance status of ECOG 0 or 1.\n* Willing to practice birth control from the time of enrollment on this study and for four months after treatment.\n* Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.\n* Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)\n* Seronegative for hepatitis B antigen and for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n* Participants must have adequate organ and marrow function as defined below:\n\n  * ANC \\> 1000\u002Fmm\\^3 without the support of filgrastim\n  * WBC \\>= 3000\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Hemoglobin \\> 8.0 g\u002Fd (Subject may be transfused to reach this cut-off)\n  * Serum ALT\u002FAST \\\u003C= 5.0 x ULN\n  * Serum creatinine \\\u003C= 1.6 mg\u002FdL\n  * Total bilirubin \\\u003C= 2.0 mg\u002FdL, except in participants with Gilbert s Syndrome, who must have a total bilirubin \\\u003C 3.0 mg\u002FdL.\n* More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment.\n\nNote: Participant may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to \\\u003C= grade 1.\n\n* Ability of subject to understand and the willingness to sign a written informed consent document.\n* Willing to sign a Durable Power of Attorney Form.\n* Subject must be co-enrolled on protocol 03-C-0277\n\nEXCLUSION CRITERIA:\n\n* Participant is nursing because of the potentially dangerous effects of the treatment on the fetus or infant.\n* Concurrent systemic steroid therapy.\n* Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.\n* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).\n* History of major organ autoimmune disease.\n* Grade 3 or 4 major organ irAEs following treatment with anti-PD-1\u002FPD-L1 monotherapy, including but not limited to myocarditis, pneumonitis, colitis, and hepatotoxicity.\n* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)\n* History of severe immediate hypersensitivity reaction to pembrolizumab or aldesleukin.\n* History of coronary revascularization or ischemic symptoms.\n* For select participants with a clinical history prompting cardiac evaluation: last known LVEF \\\u003C= 45%.\n* For select participants with a clinical history prompting pulmonary evaluation: known FEV1 \\\u003C= 50%.\n* Participant is receiving any other investigational agents.","120 Years",{"count":321,"type":21},78,[25],"Background:\n\nAldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer.\n\nObjective:\n\nTo learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer.\n\nEligibility:\n\nAdults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma.\n\nDesign:\n\nParticipants will be screened with:\n\n* Medical history\n* Physical exam\n* Electrocardiogram\n* Blood and urine tests\n* Ability to perform tasks of daily living\n* Imaging scans (CT, MRI, PET, and\u002For X-rays). They may get a contrast agent to enhance the images.\n* Photographs, if needed\n\nSome of these tests will be repeated during the study.\n\nParticipants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course.\n\nAbout 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits.\n\nParticipation will last for 5 years....",[65,325,28,326],"Advanced Locoregional Melanoma","Clear Cell Histology",[328,329],"Immunotherapy","Monoclonal Antibody","2026-05-28",{"date":332,"type":37},"2026-05-29",{"date":334,"type":37},"2022-08-18",{"date":336,"type":21},"2031-09-01",{"name":338,"class":339},"National Cancer Institute (NCI)","NIH",{"id":341,"slug":342,"hasResults":12,"nctId":343,"briefTitle":344,"officialTitle":345,"acronym":4,"eligibilityCriteria":346,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":347,"targetDuration":4,"studyType":22,"phases":349,"briefSummary":350,"conditions":351,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":355,"startDateStruct":357,"completionDateStruct":359,"leadSponsor":360,"locationsCount":213},"100459471","phase-2-trial-of-an-alternative-cabozantinib-dosing-schedule-in-metastatic-renal-cell-carcinoma-and-neuroendocrine-tumors-100459471","NCT05263050","Trial of an Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors","GU-187: Phase II Trial of Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors","Inclusion Criteria\n\n* Cohorts A and B: Histologically or cytologically confirmed advanced RCC with any clear cell or non-clear cell component. 100% sarcomatoid is permissible.\n* Cohorts A and B: Patient may have had any number of prior therapies for Cohort A, but for Cohort B patients must not have received any systemic therapy in the metastatic setting\n* Patients who have received prior (neo)adjuvant immunotherapy with pembrolizumab or similar are eligible for Cohort B IF they completed the adjuvant therapy \\> 12 months from start of trial therapy\n* Treatment naïve patients may be treated in Cohort A if deemed not candidates for nivolumab or if felt single agent cabozantinib most appropriate by the treating clinician\n* Cohort C: Well differentiated NET, grades 1-3 (any primary site) who have progressed on or are not eligible for somatostatin analogs per treating physician discretion\n* Cohort C: Disease progression within prior 12 months\n* Cohort C: Prior or concurrent treatment with somatostatin analogue allowed but no limit on lines of therapy (stable dose of somatostatin for 2 months)\n\nAll Cohorts:\n\n* At least one measurable lesion as defined by RECIST version 1.1\n* No evidence of pre-existing uncontrolled hypertension as assessed by investigator. Patients may undergo adjustments or additions to their antihypertensive regimen before or during screening to achieve optimal BP control.\n* Age \\> 18 years.\n* ECOG performance status 0 - 2\n* Patients must have normal organ and marrow function as defined below\n\n  * Leukocytes, \\> 2,000\u002FmcL\n  * Absolute neutrophil count, \\> 1,500\u002FmcL\n  * Platelets, \\> 100,000\u002FmcL\n  * Hgb, \\> 9 g\u002FdL (\\>90 g\u002FL)\n  * Total bilirubin, ≤ 1.5 x ULN (with the exception of of individuals with Gilberts syndrome who may have a bilirubin \\<3.0 mg\u002FdL)\n  * AST\u002FALT (SGOT\u002FSGPT)\u002FALP, \\< 3 x ULN ALP ≤ 5x ULN with documented bone metastases.\n  * Albumin, \\> 2.8 g\u002FdL\n  * Creatinine clearance, \\> 30 Ml\u002Fmin\u002F1.73 m2 for patients with creatinine levels above institutional normal\n  * PT\u002FINR or PTT, \\< 1.3 x the laboratory ULN\n* Ability to understand and willingness to sign a written informed consent and HIPAA consent document\n* Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment\n\nExclusion Criteria\n\n* Patients who have had systemic anti-cancer therapy or radiotherapy within 14 days or five half-lives, whichever is shorter, prior to entering the study.\n* Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Ongoing clinically relevant complications from prior radiation therapy would preclude eligibility.\n* Patients with prior therapy with cabozantinib.\n* Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to Cohort B (treatment-naïve group).\n* Cohort B only: Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger\n* Cohort B only: Patients have a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \\> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.\n* Patients may not be receiving any other investigational agents\n* History of allergic reactions or hypersensitivity attributed to compound of similar chemical or biologic composition to the agent(s) used in this study\n* Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4 inhibitors and inducers. Refer to Section 5.3.2 for detailed information. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Cardiovascular disorders:\n* Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.\n* QTcF \\> 500 msec within 28 days before first dose of study treatment.\n* Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 160 mm Hg systolic or \\> 100 mm Hg diastolic despite optimal antihypertensive treatment.\n* Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.\n* Subjects with a diagnosis of incidental, sub-segmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment.\n* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n* The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.\n* Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.\n\nNote: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.\n\n* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.\n* Lesions invading or encasing any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.",{"count":348,"type":21},111,[25],"This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors.",[28,292,352,353],"Neuroendocrine Tumors","Carcinoid Tumor","2026-05-20",{"date":356,"type":37},"2026-05-22",{"date":358,"type":37},"2022-01-21",{"date":41,"type":21},{"name":361,"class":44},"Fox Chase Cancer Center",{"id":363,"slug":364,"hasResults":12,"nctId":365,"briefTitle":366,"officialTitle":367,"acronym":368,"eligibilityCriteria":369,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":370,"targetDuration":4,"studyType":22,"phases":372,"briefSummary":373,"conditions":374,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":375,"lastUpdatePostDateStruct":376,"startDateStruct":378,"completionDateStruct":380,"leadSponsor":381,"locationsCount":383},"100582438","phase-2-trial-of-zanzalintinib-xl092-in-combination-with-immunotherapy-in-patients-who-progress-on-adjuvant-therapy-in-clear-cell-rcc-100582438","NCT06863311","Trial of Zanzalintinib (XL092) in Combination With Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCC","EXACT: Randomized Phase II Trial of Zanzalintinib (XL092) in Combination With Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCC","EXACT","Inclusion Criteria:\n\n1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.\n2. Age ≥ 18 years at the time of consent.\n3. ECOG Performance Status of 0-1 within 28 days prior to registration.\n4. Advanced or metastatic RCC with a clear cell component.\n5. Prior treatment must have included an anti-PD-1. Subjects must have progressed on or after adjuvant anti-PD-1 therapy. A washout period of 14 days prior to study treatment initiation is required. Subjects must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline. Unresolved grade 2 or greater toxicity from prior checkpoint inhibitor therapy will exclude a subject from enrolling. Subjects that received other systemic therapy after anti-PD1 are not eligible.\n6. Measurable disease per RECIST 1.1.\n7. Demonstrate adequate organ function as defined below. All screening labs are to be obtained within 2 weeks prior to registration.\n\n   * Absolute Neutrophil Count (ANC): ≥ 1500\u002Fmm3 without granulocytes colony-stimulating factor support within 2 weeks of screening laboratory collection\n   * Platelet Count (PLT): ≥ 100,000\u002Fmm3; without transfusion within 2 weeks of screening laboratory sample collection.\n   * Hemoglobin (Hgb): ≥ 9 g\u002FdL\n   * Serum Creatinine OR Calculated CrCl using Cockgroft Gault equation: Serum creatinine \\\u003C 1.5 upper limit of normal (ULN) OR calculated Cr Clearance \\>40mL\u002Fmin\n   * Urine protein-to-creatinine ratio (UPCR): ≤1mg\u002Fmg (≤ 113.2mg\u002Fmmol) creatinine\n   * Bilirubin: ≤ 1.5 × ULN (for subjects with Gilbert's disease \\\u003C 3 x ULN)\n   * Aspartate aminotransferase (AST): ≤ 3 × ULN\n   * Alanine aminotransferase (ALT): ≤ 3 × ULN\n   * Alkaline phosphatase (ALP): ≤ 3 × ULN. For subjects with documented bone metastasis ALP ≤ 5x ULN\n   * International Normalized Ratio (INR): ≤ 1.5 x ULN\n   * Activated Partial Thromboplastin Time (aPTT): ≤ 1.2 × ULN\n8. Females of childbearing potential must have a negative urine or serum pregnancy test within 2 weeks prior to registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n9. Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or to use an effective method(s) of contraception. Males able to father a child who are sexually active with female of childbearing potential must be willing to abstain from penile-vaginal intercourse or to use an effective method(s) of contraception.\n10. Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. Testing is not required at screening unless mandated by local policy.\n11. Patients with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Testing is not required at screening unless mandated by local policy.\n12. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.\n\nExclusion Criteria:\n\n1. Prior treatment with Zanzalintinib.\n2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days prior to study treatment initiation.\n3. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 28 days prior to study treatment initiation unless otherwise specified.\n4. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n\n4\\. Radiation therapy for bone metastasis within 14 days, any other radiation therapy within 28 days prior to study treatment initiation. Systemic treatment with radionuclides within 6 weeks prior to study treatment initiation. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n\n5\\. Known brain metastases or cranial epidural disease. Subjects adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 28 days prior to study treatment initiation may be eligible. NOTE: Subjects with an incidental finding of an isolated brain lesion \\\u003C 1 cm in diameter may be eligible after sponsor-investigator approval if the lesion is radiographically stable for 28 days prior to study treatment initiation and does not require treatment per Investigator judgement. NOTE: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of study treatment initiation.\n\n6\\. Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 14 days prior to study treatment initiation.\n\n7\\. Active infection requiring systemic therapy. NOTE: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.\n\n8\\. Positive TB test with active mycobacterial infection requiring systemic treatment.\n\n9\\. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).\n\n10\\. History of severe allergic anaphylactic reactions to study drug(s) or any of their excipients.\n\n11\\. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.\n\n12\\. Administration of a live, attenuated vaccine within 30 days prior to study treatment initiation.\n\n13\\. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.\n\n14\\. Prior organ allograft including allogeneic stem cell transplant\n\n15\\. Inability to swallow oral medications. 16. Uncontrolled major cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the subject a poor study candidate.\n\n17\\. Therapeutic doses of anticoagulants are not permitted in subjects with known brain metastases at study entry. NOTE: Subjects on therapeutic doses of LMWH or specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban, without known brain metastases who are on a stable dose of the anticoagulant for at least 7 days prior to randomization and without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor may be enrolled.\n\n18\\. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n• Unstable or deteriorating cardiovascular disease including but not limited to the following:\n\n* Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).\n* Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n* Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction, or other clinically significant ischemic event within 12 months before first dose.\n* Prior history of myocarditis. • Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA\u002FTIA arterial thromboembolic events within 6 months before to first dose. NOTE: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and treated with anticoagulation per standard of care before first dose of study treatment. Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the sponsor-investigator.\n\n  * Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n* Known gastric or esophageal varices\n* Tumors invading the GI-tract from external viscera.\n* Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.\n* Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic.\n* Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. NOTE: Complete healing of an intra-abdominal abscess must be confirmed before first dose.\n\n  * Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.\n  * Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.\n  * Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. NOTE: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava) may be eligible following sponsor-investigator approval.\n\n    19\\. Other clinically significant disorders such as:\n  * Any active, known or suspected autoimmune disease. NOTE: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n  * Any condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 2 weeks of first dose of study treatment. NOTE: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Transient short-term use of systemic corticosteroids for allergic conditions (eg, contrast allergy) is also allowed.\n  * Malabsorption syndrome.\n  * Serious non-healing wound\u002Fulcer\u002Fbone fracture. NOTE: Non-healing wounds or ulcers are permitted if due to tumor- associated skin lesions.\n  * Pharmacologically uncompensated, symptomatic hypothyroidism.\n  * Moderate to severe hepatic impairment (Child-Pugh B or C).\n  * Requirement for hemodialysis or peritoneal dialysis.\n  * History of life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4, or anti-PD-1\u002FPD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to recur and manageable by standard of care treatment (eg, hypothyroidism).\n\n    20\\. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose. Prior laparoscopic nephrectomy within 4 weeks prior to first dose. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose. NOTE: Fresh tumor biopsies should be performed at least 7 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.\n\n    21\\. Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 450 ms for males or \\> 470 ms for females per electrocardiogram (ECG) within 14 days before first dose of study treatment. NOTE: If a single ECG shows a QTcF with an absolute value \\> 450 ms for males or \\> 470 ms for females, two additional ECGs at intervals of approximately 3 minutes must be performed within 30 minutes after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.\n\n    22\\. Subjects with inadequately treated adrenal insufficiency.",{"count":371,"type":21},70,[25],"The study population for this Phase 2 study will include men and women ≥ 18 with confirmed renal cell carcinoma who have progressed on adjuvant anti-PD-1\u002FPD-L1 therapy, the current standard of care. Subjects will be randomized to Arm A or Arm B. Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of zanzalintinib (XL092) alone and will be taken once daily continuously (Day 1-Day 28). Arm B treatment will consist of XL092 plus nivolumab. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.",[233,28,291],"2026-05-15",{"date":377,"type":37},"2026-05-18",{"date":379,"type":37},"2026-03-13",{"date":242,"type":21},{"name":382,"class":44},"Karie Runcie",4,{"id":385,"slug":386,"hasResults":12,"nctId":387,"briefTitle":388,"officialTitle":389,"acronym":4,"eligibilityCriteria":390,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":391,"targetDuration":4,"studyType":22,"phases":393,"briefSummary":394,"conditions":395,"keywords":398,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":400,"lastUpdatePostDateStruct":401,"startDateStruct":402,"completionDateStruct":404,"leadSponsor":406,"locationsCount":213},"100493077","phase-1-drug-screening-using-novel-imd-in-renal-cell-carcinoma-100493077","NCT05700461","Drug Screening Using Novel IMD in Renal Cell Carcinoma","Pilot Study of an Implantable Microdevice for in Situ Evaluation of Drug Response in Renal Cell Carcinoma","Inclusion Criteria:\n\n* Patients must have the ability to understand and the willingness to sign a written informed consent document.\n* Participants must have confirmed or suspected localized or metastatic renal cell carcinoma, and must be planned for either nephrectomy or metastatectomy as part of their clinical care. The lesion planned for excision must be at least 1cm in size.\n* Participants must be 18 years of age or older.\n* Participants must be evaluated by a medical oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease.\n* Patients must be deemed medically stable to undergo both percutaneous procedures and standard-of-care surgical procedures.\n* Participants will undergo laboratory testing within 30 days prior to the procedure (or within 72 hours if there has been a change in the clinical status since the initial blood draw). Patients must have absolute neutrophil count ≥1,000\u002FmcL, platelets ≥50,000\u002FmcL, INR \\\u003C 1.5 and PTT \\\u003C1.5x control.\n* Participants must have undergone CT or MRI that assesses the extent of disease and allows the research team to assess for study eligibility. This will have been done as part of the standard-of-care.\n* The participant's case must be reviewed by representatives of interventional radiology and the appropriate surgical subspecialty to assess the following factors:\n* Patient is clinically stable to undergo microdevice implantation and surgical procedures\n* Patient has sufficient volume of disease to allow implantation of the microdevice\n* Patient has a lesion for which the microdevice is a) amenable to percutaneous placement, and b) amenable to removal at the time of surgery\n* Patients must be willing to undergo research-related genetic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories.\n\nExclusion Criteria\n\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit the safety of a biopsy and\u002For surgery.\n* Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures (detailed below).",{"count":392,"type":21},20,[24],"This research is being done to study the safety and feasibility of implanting and retrieving a microdevice that releases microdoses of 19 specific drugs or drug combinations as a possible tool to evaluate the effectiveness of several cancer drugs against metastatic renal cell carcinoma (RCC).\n\nThe name of the intervention(s) involved in this study are:\n\n* Implantable Microdevice (IMD)\n* Surgery (excision of tumor)\n* Drugs used in this study will only include drugs already used as standard of care for the treatment of metastatic renal cell carcinoma (RCC)",[396,28,397],"Renal Cell Carcinoma","Kidney Cancer",[396,28,397,399],"Suspected Renal Cell Carcinoma","2026-05-14",{"date":377,"type":37},{"date":403,"type":37},"2024-12-01",{"date":405,"type":21},"2029-08-31",{"name":407,"class":44},"Oliver Jonas",{"id":409,"slug":410,"hasResults":12,"nctId":411,"briefTitle":412,"officialTitle":413,"acronym":414,"eligibilityCriteria":415,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":416,"targetDuration":4,"studyType":22,"phases":417,"briefSummary":418,"conditions":419,"keywords":4,"overallStatus":428,"whyStopped":4,"lastUpdateSubmitDate":429,"lastUpdatePostDateStruct":430,"startDateStruct":432,"completionDateStruct":434,"leadSponsor":436,"locationsCount":213},"100596296","phase-2-zanzalintinib-for-metastatic-clear-cell-renal-cell-carcinoma-with-bone-metastases-100596296","NCT07043608","Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases","A Phase II Study of Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases in Patients Previously Treated With Immune Checkpoint Inhibitors","ZAMBONI","Inclusion Criteria:\n\n1. Participants must have unresectable advanced or metastatic RCC with a predominant clear cell histologic component .\n2. At least three bone metastases are present and detectable on bone scan, and at least one bone metastasis is NOT planned to be treated with radiation therapy.\n3. Previously treated with 1-3 prior lines of therapy in at least one of the following settings:\n\n   1. Metastatic setting; must have received combination therapy containing either programmed cell death protein 1 (PD-1) inhibitor\u002Fcytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or PD-1 inhibitor\u002Fvascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKI).\n   2. Adjuvant setting; must have received pembrolizumab and have had documented progression of disease within 1 year of the first dose of pembrolizumab .\n4. Age ≥18 years.\n5. Has seen a dentist within 90 days prior to enrollment and been cleared to receive bone-strengthening agents.\n6. Availability of a representative formalin fixed, paraffin embedded tumor specimen or fresh frozen tissue specimen that enables the definitive diagnosis of RCC, accompanied by an associated pathology report. If stored specimens are not available, an optional biopsy may be performed and specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion.\n7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n8. Demonstrates adequate organ function as defined below within 14 days prior to first study treatment:\n\n   1. Absolute neutrophil count (ANC) \\>=1,500\u002F μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1).\n   2. Platelets ≥100,000\u002F μL (without transfusion within 2 weeks prior to Cycle 1, Day 1).\n   3. White Blood Cell count (WBC) counts ≥ 2500\u002FμL.\n   4. Lymphocyte count ≥ 500\u002FμL.\n   5. Hemoglobin ≥9.0 g\u002FdL.\n\n      Participants may be transfused or receive erythropoietic treatment to meet this criterion:\n   6. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN). Participants with known Gilbert disease who have serum bilirubin level \\\u003C= 3 x ULN may be enrolled.\n   7. Aspartate aminotransferase (AST)\u002Fserum glutamic-oxaloacetic transaminase (SGOT) ≤2.5 X institutional upper limit of normal.\n   8. Alanine aminotransferase (ALT)\u002Fserum glutamic-pyruvic transaminase (SGPT) ≤2.5 X institutional upper limit of normal.\n   9. Alkaline phosphatase ≤2.5 X institutional upper limit of normal. For participants with documented liver metastases: AST and\u002For ALT ≤ 5 x ULN. For participants with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN.\n   10. Creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine clearance ≥ 40 mL\u002Fmin by institutional standard AND urine protein-creatinine ratio (UPCR) 1mg\u002Fmg.\n   11. International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose.\n   12. Serum ionized calcium above lower limit of normal and ≤ 1.5 x ULN.\n9. If any Grade ≥1 toxicities occurred in relation to prior treatment, patients must have recovered to baseline or ≤ Grade 1 unless adverse events are clinically insignificant or stable on supportive medication if needed.\n10. Ability to understand and the willingness to sign a written informed consent document.\n11. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n12. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n13. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n14. Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix 4) during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.\n\n    a. Through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men.\n15. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \\\u003C 55 years-of-age must have a serum follicle stimulating hormone (FSH) level \\> 40 milli-international units per millilitre (mIU\u002FmL) to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. Exception: women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and\u002For uterus).\n\nExclusion Criteria:\n\n1. Prior treatment with zanzalintinib for RCC.\n2. Receipt of any small molecule kinase inhibitor (including investigational) or vascular endothelial growth factor (VEGF)-targeted therapy within 2 weeks before the first dose of study treatment.\n3. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.\n4. Participants requiring whole brain radiotherapy (WBRT).\n5. Incomplete healing from prior radiotherapy as determined by the treating radiation oncologist or treating investigator.\n6. Participation in an experimental drug study within 28 days of study enrollment.\n7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.\n8. Pregnant and lactating women are excluded from this study because zanzalintinib is an investigational product with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanzalintinib, breastfeeding should be discontinued if the mother is treated with zanzalintinib.\n9. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.\n10. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation); Clinically significant hematuria, hematemesis, or hemoptysis of \\>0.5 tsp (2.5ml) of red blood or other history of significant bleeding within 12 weeks before first dose of study treatment.\n11. Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.\n12. Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.\n13. Concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, factor Xa inhibitor betrixaban, or platelet inhibitors. Other anticoagulants are allowed.\n\n    1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n    2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n\n    i. Participants who have known brain metastases and who require therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban are not eligible for this study.\n\n    ii. Participants with known brain metastases and who are taking prophylactic low-dose aspirin for cardioprotection or low-dose (prophylactic-dose) low molecular weight heparin are eligible.\n\n    Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.\n14. Previously identified allergy or hypersensitivity to components of the treatment.\n15. Malignancy that requires anti-cancer directed therapy within the last 3 years. Exceptions include those cancers that are considered cured by local therapy (e.g. Basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of breast, bladder, or cervix) or other cancers that have low malignant potential and do not require systemic therapy (e.g. Gleason grade \\\u003C6 prostate adenocarcinoma).\n16. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.\n17. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n18. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.\n19. Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.\n20. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n    1. Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).\n    2. Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n    3. Stroke (including transient ischemic attack (TIA)), myocardial infarction, or other clinically significant arterial thrombotic and\u002For ischemic event within 6 months before first dose of study treatment.\n    4. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.\n\n       Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n\n       Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.\n    5. Prior history of myocarditis.\n    6. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n\n    i. Tumors invading the GI-tract from external viscera. ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.\n\n    iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic.\n\n    iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.\n\n    v. Known gastric or esophageal varices. vi. Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks.\n21. Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.\n22. Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).\n23. Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior V. cava) may be eligible following Principal Investigator approval.\n24. Other clinically significant disorders that would preclude safe study participation.\n\n    1. Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.\n    2. Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for subjects meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) Cluster of differentiation 4 positive (CD4+) T cell count ≥ 200\u002FµL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking Cytochrome P450, family (CYP) inhibitors (e.g., zidovudine, ritonavir, cobicistat, didanosine) or Cytochrome P450, family 3 (CYP3) inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider.\n    3. Serious non-healing wound\u002Fulcer\u002Fbone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.\n\n    i. Complete healing of intra-abdominal abscess must be confirmed before the first dose of study treatment d. Malabsorption syndrome. e. Pharmacologically uncompensated, symptomatic hypothyroidism. f. Moderate to severe hepatic impairment (Child-Pugh B or C). g. Requirement for hemodialysis or peritoneal dialysis. h. History of solid organ or allogeneic stem cell transplant.\n25. Major surgery (as defined in Section 6.6.2.3; e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (i.e. nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (e.g., simple excision, tooth extraction) within 5 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.\n\n    Note: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.\n26. Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.\n\n    Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.\n27. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.\n28. Patients who are ineligible for CT contrast AND who are unable to undergo MRI for any reason.\n29. Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.\n30. Other conditions, which in the opinion of the Investigator, would compromise the safety of the participant or the participant's ability to complete the study.",{"count":392,"type":21},[25],"This is a single-institution, phase 2 trial of zanzalintinib plus investigator-choice bone-strengthening agent in patients with metastatic renal cell carcinoma (RCC) with bone metastases whose disease has advanced on 1-3 prior lines of therapy, including at least one immune oncology-based (IO) therapy in the adjuvant or first-line metastatic setting.",[420,421,422,423,424,291,425,426,28,427],"Clear Cell Renal Cell Cancer (ccRCC)","Clear Cell Renal Carcinoma","Clear Cell Renal Cell Carcinoma Metastatic","Clear Cell Renal Cancer","Bone Metastases of a Malignant Tumor","Bone, Metastatic Cancer","Metastatic Cancer","Metastases to Bone","NOT_YET_RECRUITING","2026-04-27",{"date":431,"type":37},"2026-05-01",{"date":433,"type":21},"2026-05-30",{"date":435,"type":21},"2030-02-28",{"name":437,"class":44},"Kelly Fitzgerald, MD",{"id":439,"slug":440,"hasResults":12,"nctId":441,"briefTitle":442,"officialTitle":443,"acronym":4,"eligibilityCriteria":444,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":445,"targetDuration":4,"studyType":22,"phases":447,"briefSummary":449,"conditions":450,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":464,"lastUpdatePostDateStruct":465,"startDateStruct":467,"completionDateStruct":469,"leadSponsor":471,"locationsCount":213},"100415725","cryoablation-combined-with-stereotactic-body-radiation-therapy-for-the-treatment-of-painful-bone-metastases-the-crome-trial-100415725","NCT04693377","Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial","Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases","Inclusion Criteria:\n\n* Patient must have a primary diagnosis of malignancy and radiographic evidence of bone metastases. Eligible tumor histologies include the following malignancies with low alpha\u002Fbeta ratios: renal cell carcinoma, urothelial carcinomas, castration-resistant prostate cancer, sarcoma, thyroid carcinoma, colorectal carcinoma, and melanoma\n* A target lesion the meets the following criteria:\n\n  * The target lesion must be amenable to both cryoablation and SBRT, as determined by the study principal investigators (PIs)\n  * The target lesion must be =\\\u003C 7cm\n  * The pain due to the target lesion must be at least 4\u002F10 based on the BPI pain scale\n  * Pain from the metastatic site must correlate with an identifiable tumor on computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US) imaging\n* Life expectancy \\>= 3 months\n* Platelet count \\> 50,000\u002Fmm\\^3 within 6 weeks of screening\n* International normalized ratio (INR) \\\u003C 1.5 within 6 weeks of screening\n* If taking antiplatelet or anticoagulation medication, it must be able to be discontinued 48 hours prior to the procedure or at the discretion of the PI (e.g., aspirin, ibuprofen, low molecular weight heparin \\[LMWH\\] preparations)\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%) within 6 weeks of screening\n* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women \\\u003C 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization. Women \\>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\> 1 year ago, had chemotherapy-induced menopause with last menses \\> 1 year ago, or underwent surgical sterilization\n* All lines of prior systemic therapy are permissible. Standard concurrent chemotherapy, immunotherapy, or targeted therapy are permissible\n* Ability to understand and the willingness to sign a written informed consent document\n\nExclusion Criteria:\n\n* Prior locoregional therapy to target lesion, including ablation of any modality, embolization, radiation, or surgery\n* Patient may not be receiving any other investigational agents. Standard concurrent chemotherapy, immunotherapy, or targeted therapy will be allowed\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant or nursing women; women of childbearing potential unless using effective contraception as determined by the investigator\n* Target lesions that involve the spinal column or calvarium\n* Absolute neutrophil count \\\u003C 1000 mm\\^3 within 6 weeks of screening\n* Active infection\n* Presence of confirmed pathologic fracture at the target lesion not amenable to percutaneous stabilization\n* Lesions that involve a weight-bearing long bone of the lower extremity with the tumor causing \\> 50% loss of cortical bone. Lesions involving the hands and feet",{"count":446,"type":21},40,[448],"NA","This trial compares cryoablation combined with stereotactic body radiation therapy to stereotactic body radiation therapy alone to see how well they work in treating patients with pain from cancer that has spread to the bones (bone metastases). Bone is a common site of metastasis in advanced cancer, and bone metastases often result in debilitating cancer-related pain. The current standard of care to treat painful bone metastases is radiation therapy alone. However, many patients do not get adequate pain relief from radiation therapy alone. Another type of therapy that may be used to provide pain relief from bone metastases is cryoablation. Cryoablation is a procedure in which special needles are inserted into the tumor site. These needles grow ice balls at their tips to freeze and kill cancer cells. The goal of this trial is to compare how well cryoablation in combination with radiation therapy works to radiation therapy alone when given to cancer patients to provide pain relief from bone metastases.",[451,452,453,64,65,454,28,455,456,158,457,458,67,459,460,461,462,463],"Castration-Resistant Prostate Carcinoma","Metastatic Colorectal Carcinoma","Metastatic Malignant Neoplasm in the Bone","Metastatic Prostate Carcinoma","Metastatic Sarcoma","Metastatic Thyroid Gland Carcinoma","Stage IV Colorectal Cancer AJCC v8","Stage IV Prostate Cancer AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVA Prostate Cancer AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVB Prostate Cancer AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2026-04-10",{"date":466,"type":37},"2026-04-15",{"date":468,"type":37},"2021-03-16",{"date":470,"type":21},"2027-04-01",{"name":472,"class":44},"M.D. Anderson Cancer Center",{"id":474,"slug":475,"hasResults":12,"nctId":476,"briefTitle":477,"officialTitle":478,"acronym":4,"eligibilityCriteria":479,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":480,"targetDuration":4,"studyType":22,"phases":481,"briefSummary":482,"conditions":483,"keywords":4,"overallStatus":428,"whyStopped":4,"lastUpdateSubmitDate":484,"lastUpdatePostDateStruct":485,"startDateStruct":487,"completionDateStruct":489,"leadSponsor":491,"locationsCount":213},"100631450","fasting-mimicking-diet-combined-with-io-tki-combination-therapy-in-patients-with-metastatic-renal-cell-carcinoma-100631450","NCT07500831","Fasting-Mimicking Diet Combined With IO-TKI Combination Therapy in Patients With Metastatic Renal Cell Carcinoma","Fasting-Mimicking Diet Combined With Toripalimab Plus Axitinib for Metastatic or Unresectable Renal Cell Carcinoma: A Single-Arm, Open-Label, Single-Center Clinical Trial","Inclusion Criteria:\n\n1. Subjects voluntarily participate in the study and sign the informed consent form.\n2. Age ≥ 18 years at the time of signing the informed consent form; males or females are eligible.\n3. Pathologically confirmed advanced renal cell carcinoma (metastatic or unresectable) with predominant clear cell histology.\n4. No prior systemic anti-tumor therapy (except for cytokine therapy).\n5. At least one measurable target lesion according to RECIST v1.1 criteria (confirmed by CT or MRI).\n6. Body mass index (BMI) ≥ 20 kg\u002Fm².\n7. IMDC intermediate- or poor-risk group.\n8. Willing and able to comply with the fasting-mimicking diet (FMD)protocol,scheduled visits, treatment plan, laboratory tests, and other study procedures.\n9. Able to maintain daily contact with the investigator (via telephone or email) to communicate key clinical information, including daily body weight, blood pressure, health status, and adverse events during the 5-day FMD period.\n10. Low nutritional risk according to the Nutritional Risk Screening (NRS) tool.\n11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n12. Adequate organ function within 7 days prior to the first dose of study drug (no blood products, hematopoietic growth factors, leukocyte- or platelet-stimulating agents allowed in the 7 days prior to laboratory testing):\n\n    Absolute neutrophil count ≥ 1.5 × 10⁹\u002FL Platelets ≥ 100 × 10⁹\u002FL Hemoglobin ≥ 90 g\u002FL Serum albumin ≥ 30 g\u002FL AST and ALT ≤ 2.5 × upper limit of normal (ULN); if liver metastases are present, AST and ALT ≤ 5 × ULN Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN allowed for subjects with Gilbert syndrome) Serum creatinine ≤ 1.5 × ULN; if \\> 1.5 × ULN, creatinine clearance (CLcr) calculated by Cockcroft-Gault formula must be ≥ 50 mL\u002Fmin Left ventricular ejection fraction (LVEF) \\> 50% Proteinuria \\\u003C 2+ (if ≥ 2+, 24-hour urine protein quantification must be \\\u003C 1 g) International normalized ratio (INR) ≤ 1.5 × ULN or prothrombin time (PT) prolongation ≤ 1.5 × ULN; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN\n13. No plans for pregnancy during the study period.\n\nExclusion Criteria:\n\n1. Prior receipt of any systemic anti-tumor therapy for renal cell carcinoma (RCC), including systemic chemotherapy, anti-angiogenic therapy, molecular targeted therapy, immunotherapy containing anti-CTLA-4, anti-PD-1\u002FPD-L1 monoclonal antibodies, and immune checkpoint agonist antibodies (e.g., anti-ICOS, anti-CD40, anti-CD137, anti-GITR, or anti-OX40 antibodies).\n2. Unintentional weight loss ≥5% within the past 3 months, unless the patient has BMI \\>22 kg\u002Fm² and weight loss at study entry is \\\u003C10%; or unintentional weight loss ≥10% within the past 3 months, unless the patient has BMI \\>25 kg\u002Fm² and weight loss at study entry is \\\u003C15% (in both cases, body weight must have been stable for at least 1 month prior to study entry).\n3. Body mass index (BMI) \\\u003C20 kg\u002Fm².\n4. Moderate or high nutritional risk according to the Nutritional Risk Screening (NRS) assessment.\n5. Severe food allergy that prevents the subject from consuming the foods required for the fasting-mimicking diet (FMD).\n6. Symptomatic central nervous system (CNS) metastases, leptomeningeal metastases, or spinal cord compression due to metastases prior to the first dose of study treatment. Exception: Patients with symptomatic CNS metastases who have received treatment and are stable for ≥4 weeks (stable defined as no radiographic progression and resolution of metastasis-related symptoms) and have discontinued systemic corticosteroids (any dose), anticonvulsants, and mannitol for \\>2 weeks may be enrolled.\n7. History of other malignancies within 5 years prior to signing the informed consent form (except for cured basal cell skin carcinoma, papillary thyroid carcinoma, etc.).\n8. Active autoimmune disease requiring systemic treatment (e.g., corticosteroids or immunosuppressants) within the past 2 years prior to the first dose of the combination therapy.\n9. Any serious concomitant disease, as judged by the investigator, that may endanger the subject's safety or interfere with the subject's ability to complete the study.\n10. Receiving long-term systemic corticosteroid therapy (daily dose \\>10 mg prednisone equivalent) within 7 days prior to the first dose of the combination therapy.\n11. Any of the following cardiovascular diseases:\n\n    Acute myocardial infarction within 6 months prior to the first dose of the combination therapy.\n\n    History of and\u002For current New York Heart Association (NYHA) Class III or IV heart failure.\n\n    Poorly controlled cardiovascular disease, including angina, pulmonary hypertension, or severe cardiac rhythm or conduction abnormalities.\n\n    Mean QT interval corrected by Fridericia's formula (QTcF) \\>450 ms (male) or \\>470 ms (female) on 12-lead electrocardiogram (ECG) prior to the first dose of the combination therapy.\n12. Known history of substance abuse of psychotropic medications, alcohol abuse, or drug abuse; or history of definite neurological or psychiatric disorders, including epilepsy, dementia, or hepatic encephalopathy.\n13. Participation in another clinical study and receipt of other investigational therapy within 4 weeks prior to the first dose of the combination therapy.\n14. Major surgery within 4 weeks prior to the first dose of the combination therapy (adequate wound healing after major surgery must be clinically assessed).\n15. Arteriovenous thromboembolic events within 6 months prior to the first dose of the combination therapy, including cerebrovascular accident, history of stroke or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other serious thromboembolic events.\n16. Any patient, as judged by the investigator, who may increase the risk associated with the study, interfere with the interpretation of study results, or is deemed unsuitable for enrollment by the investigator and\u002For sponsor.",{"count":20,"type":21},[448],"This study is testing whether adding a 5-day fasting-mimicking diet (FMD) can help people with advanced kidney cancer when given together with standard first-line cancer medicines.",[288,28,233],"2026-03-24",{"date":486,"type":37},"2026-03-30",{"date":488,"type":21},"2026-04",{"date":490,"type":21},"2029-04",{"name":492,"class":44},"Qilu Hospital of Shandong University",{"id":494,"slug":495,"hasResults":12,"nctId":496,"briefTitle":497,"officialTitle":498,"acronym":499,"eligibilityCriteria":500,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":319,"enrollmentInfo":501,"targetDuration":4,"studyType":22,"phases":502,"briefSummary":503,"conditions":504,"keywords":507,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":484,"lastUpdatePostDateStruct":509,"startDateStruct":510,"completionDateStruct":512,"leadSponsor":514,"locationsCount":213},"100346136","phase-2-study-of-olaparib-in-metastatic-renal-cell-carcinoma-patients-with-dna-repair-gene-mutations-100346136","NCT03786796","Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations","Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID)","ORCHID","Inclusion Criteria:\n\n* Willing and able to provide written informed consent. Provision of informed consent is required prior to any study procedures.\n* Patients aged 18 years of age or older.\n* Histological proof of renal cell carcinoma (both clear cell and non-clear cell allowed).\n* Metastatic (AJCC Stage IV) renal cell carcinoma.\n* Somatic or germline mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L as documented by a clinical CLIA-grade, tissue, saliva or blood-based genetic test.\n* At least one prior treatment with an anti-angiogenic agent or immune checkpoint inhibitor.\n* Any number of prior systemic therapies is allowed (cytokine, anti-angiogenic, mTOR, immune checkpoint blockage or clinical trial).\n* Must have measurable disease as defined by RECIST 1.1 criteria.\n* Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:\n\n  * Hemoglobin ≥ 10.0 g\u002FdL with no blood transfusion in the past 28 days\n  * Absolute neutrophil count (ANC) ≥ 1.5 x 10\\^9\u002FL\n  * Platelet count ≥ 100 x 10\\^9\u002FL\n  * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)\n  * Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) \u002F Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5 x ULN.\n\nNote: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.\n\n* Patients must have a creatinine clearance ≥ 40 mL\u002Fmin calculated by Cockroft-Gault formula or 24 hour urine test.\n* ECOG PS ≤ 1.\n* Participants must have a life expectancy ≥ 16 weeks.\n* Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.\n\nPostmenopausal is defined as:\n\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.\n* Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 years old.\n* Radiation-induced oophorectomy with last menses \\> 1 year ago.\n* Chemotherapy-induced menopause with \\> 1 year interval since last menses.\n* Surgical sterilization (bilateral oophorectomy or hysterectomy).\n* Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.\n\nExclusion Criteria:\n\n* Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy \\> 3 years prior to registration, and that the patient remains free of recurrent or metastatic disease.\n* Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.\n* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).\n* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.\n* Breast feeding women.\n* Use of any prohibited concomitant medications within the prior 2 weeks.\n* Involvement in the planning and\u002For conduct of the study (applies to both AstraZeneca staff and\u002For staff at the study site).\n* Participation in another clinical study with an investigational product during the last 2 weeks.\n* Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.\n* Any previous treatment with PARP inhibitor, including olaparib.\n* Resting ECG with QTc \\> 500 ms and\u002For indication of uncontrolled cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, electrolyte disturbances, etc.), or patients with congenital and\u002For family history of long QT syndrome.\n* Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. During the study, if co-administration of a strong or moderate inhibitor is required because there is no suitable alternative medication, exception to this criterion may be allowed with a suitable dose reduction of olaparib.\n* Concomitant use of known strong CYP3A inducers (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital or enzalutamide and 3 weeks for other agents.\n* Persistent toxicities (\\> Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.\n* Patients with myelodysplastic syndrome (MDS)\u002Facute myeloid leukemia (AML) or with features suggestive of MDS\u002FAML.\n* Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.\n* Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.\n* Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.\n* Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).\n* Known hypersensitivity to olaparib or any of the excipients of the product.\n* Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.\n* No packed red blood cells and\u002For platelet transfusions within the last 28 days prior to study entry.",{"count":392,"type":21},[25],"Single arm, single site, open-label Phase II study of the effects of oral olaparib in participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L who have had prior treatment with at least one immune checkpoint inhibitor or anti-VEGF therapy. Must have measurable disease on CT imaging per RECIST 1.1 criteria.",[396,28,397,505,506],"Renal Carcinoma","Kidney Cancer Metastatic",[508],"Olaparib",{"date":486,"type":37},{"date":511,"type":37},"2019-06-03",{"date":513,"type":21},"2028-03",{"name":515,"class":44},"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins",{"id":517,"slug":518,"hasResults":12,"nctId":519,"briefTitle":520,"officialTitle":521,"acronym":522,"eligibilityCriteria":523,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":524,"targetDuration":4,"studyType":22,"phases":525,"briefSummary":526,"conditions":527,"keywords":530,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":533,"lastUpdatePostDateStruct":534,"startDateStruct":536,"completionDateStruct":538,"leadSponsor":540,"locationsCount":542},"100602406","phase-2-a-study-of-sasanlimab-palbociclib-and-axitinib-in-metastatic-renal-cell-carcinoma-100602406","NCT07123090","A Study of Sasanlimab, Palbociclib and Axitinib in Metastatic Renal Cell Carcinoma","A Phase 2 Study of Sasanlimab, Palbociclib and Axitinib in Metastatic Renal Cell Carcinoma - SPARCC","SPARCC","Inclusion Criteria:\n\n* Histologically or cytologically confirmed unresectable advanced or metastatic renal cell carcinoma with a clear cell component or translocation renal cell carcinoma. Patients with clear cell carcinoma and sarcomatoid histology are eligible.\n\n  * a. For tRCC please refer to the following for eligibility definitions:\n\n    * i. TFE3 (Xp11.2) translocation RCC: confirmed by IHC; however, FISH should be utilized if IHC is not optimal (ie, conclusive) or unavailable.\n    * ii. TFEB rearranged RCC: confirmed by FISH; TFEB amplified tumors are excluded.\n  * b. A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy obtained during screening will be required (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides from a primary or metastatic tumor resection or biopsy) can be provided if the following criteria are met:\n\n    * i. The biopsy or resection was performed within 1 year of registration AND\n    * ii. The patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and registration onto the current study. If an FFPE tissue block cannot be provided as per documented regulations then 15 unstained slides (10 minimum) will be acceptable\n  * c. Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided as per documented regulations, then 15 unstained slides (10 minimum) will be acceptable.\n* Measurable disease as per RECIST 1.1. See Section 11 for the evaluation of measurable disease.\n* Age ≥ 18 years.\n* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).\n* Normal organ and marrow function as defined below:\n\n  * a. Absolute neutrophil count ≥1.5×109\u002FL\n  * b. Platelets ≥100×109\u002FL\n  * c. Hemoglobin ≥9g\u002FdL (RBC transfusions allowed)\n  * d. Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) with the following exception: patients with known Gilbert disease should have a total serum bilirubin ≤ 3 x ULN\n  * e. AST(SGOT)\u002FALT(SGPT) ≤1.5 × ULN\n  * f. Creatinine clearance ≥30 mL\u002Fmin according to the CKD-EPI equation. (APPENDIX C)\n  * g. Urine protein \\\u003C1+ by urinalysis; If ≥1+ protein or otherwise suggestive of any proteinuria above a trace amount (per local institutional standards), a random urine protein and creatinine ratio (UPCR) should be collected. A 24-hour urine collection can also be utilized for direct measurement. When multiple modalities are used, the 24-hour urine measurement takes precedence over the random UPCR; refer to section 6.2 for further guidance.\n* Women of child-bearing potential and men must agree to use adequate contraception (intrauterine device or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. A negative pregnancy serum test should be obtained within 7 days of therapy initiation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation. Participants treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of sasanlimab, axitinib and palbociclib administration.\n* Ability to swallow oral medications.\n* Ability to understand and willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Treatment with the following prior therapies:\n\n  * a. Prior systemic therapy for advanced or metastatic RCC.\n  * b. Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred within 12 months of last dose of such therapy. Treatment with an immune checkpoint inhibitor in the adjuvant setting is allowed providing more than 12 months have elapsed since last dose or completion of therapy.\n  * c. Prior treatment with any immunotherapeutic agent (IL-2, IFN-α, anti-PD(L)-1, anti-CTLA-4, or any other antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways).\n  * d. Prior therapy with axitinib or other therapies targeting VEGF pathway in the metastatic setting (adjuvant therapy is allowed).\n\n    e. Prior therapy with any CDK4\u002F6 inhibitor.\n* Participants with untreated brain metastases. Participants with metastatic CNS tumors may participate in this trial, if the participant is ≥ 4 weeks from therapy completion (incl. radiation and\u002For surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy \\>10 mg\u002Fday prednisone equivalents. A repeat MRI or CT brain to show stability is required.\n* Wide field radiation therapy ≤ 2 weeks prior to treatment start. Prior palliative radiotherapy to metastatic non-target lesion(s) is permitted if completed at least 48hrs prior to patient registration.\n* Untreated deep vein thrombosis or pulmonary embolism, or event of deep vein thrombosis or pulmonary embolism within 2 weeks of treatment start. Patient should be on at least 1 week of anticoagulation before C1D1.\n* Major surgery\u002Fsurgical procedures within the past 4 weeks prior to registration.\n* The patient has serious and\u002For uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease - also see 3.2.22, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \\[e.g. estimated creatinine clearance \\\u003C30ml\u002Fmin\\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).\n* Current or prior use of immunosuppressive medication within 7 days prior to registration, except the following:\n\n  * a. Intranasal, inhaled, topical steroids, or local steroid injections (eg. intra-articular injection).\n  * b. Systemic corticosteroids at physiologic doses ≤10 mg\u002Fday of prednisone or equivalent.\n  * c. Steroids as premedication for hypersensitivity reactions (eg. CT scan premedication).\n* Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3) or any history of anaphylaxis.\n* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment are eligible.\n* Vaccination within 4 weeks of the first dose of sasanlimab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza or shingles vaccines). Note, the COVID19 vaccine is not a live vaccine and permitted.\n* Grade ≥3 hemorrhage within 4 weeks of registration.\n* Patient with active systemic bacterial infection (requiring IV antibiotics at the time of initiating study treatment), fungal infection, or detectable viral infection. Patients with known viral infection (such as HIV) are excluded given the potential for interactions between antiretroviral agents and palbociclib and axitinib, and the potential for increased risk of life-threatening infection with therapy that is myelosuppressive. If patients are not known to have HIV, a HIV test is required prior to registration.\n* Patients with known Hepatitis B or Hepatitis C infection are excluded only if there is evidence of active infection (detectable Hepatitis B surface antigen, detectable HBV DNA, or detectable Hepatitis C RNA).\n* Prior allogenic or autologous stem cell or any solid organ transplant.\n* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).\n* Participants who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant. Therapeutic use of low molecular weight heparin and factor Xa inhibitors (eg. apixaban, rivaroxaban) is permitted.\n* Other malignancy diagnosed within 2 years of treatment start unless negligible risk of metastases or death according to the investigator (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact patients 5-year life expectancy).\n* Has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), myocarditis, sudden cardiac arrest.\n* Has had any major cardiovascular event within 6 months prior to treatment start, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic event or New York Heart Association Class III or IV heart failure.\n* Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2 or history of long QTC syndrome. Any history of myocarditis.\n* History of interstitial lung disease or other restrictive lung disease, as well as history of symptomatic respiratory condition considered clinically significant by the investigator. Individuals with a history of radiotherapy to the thorax and any history of pneumonitis will be excluded.\n* Current or past tobacco users with a history of cigarette smoking greater than 30 pack-yrs (i.e., # of packs of cigarettes smoked per day × # of years patient has smoked \\> 30).\n* Participants with a known hypersensitivity to the study compounds or to its excipients.\n* Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4\u002F5 inhibitors, including their administration within 7 days prior to treatment start (eg. Grapefruit juice or grapefruit\u002Fgrapefruit-related citrus fruits \\[eg. Seville oranges, pomelos\\], ketoconazole, miconazole, itraconazole, voriconazole, , clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.\n* Current use or anticipated need for drugs that are known strong CYP3A4\u002F5 inducers, including their administration within 14 days prior to treatment start (eg. Phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, 23albociclib, clevidipine, St John's wort).\n* Participants who have taken herbal medications within 7 days prior to treatment start. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.\n* Females that are pregnant or breastfeeding.\n* Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.",{"count":7,"type":21},[25],"The goal of this research study is to evaluate how well and safely the study drugs sasanlimab, palbociclib, and axitinib work for treatment of participants with advanced clear cell renal cell carcinoma (ccRCC) or translocation renal cell carcinoma (tRCC).\n\nThe name of the study drugs involved in this research study is:\n\n* Sasanlimab (a type of monoclonal antibody)\n* Palbociclib (a type of kinase inhibitor)\n* Axitinib (a type of Vascular endothelial growth factor inhibitor)",[28,528,396,529,397,29],"Metastatic Renal Cancer","Advanced Clear Cell Renal Cell Carcinoma",[28,528,396,529,397,29,531,532],"ccRCC","tRCC","2026-03-23",{"date":535,"type":37},"2026-03-25",{"date":537,"type":37},"2025-11-24",{"date":539,"type":21},"2028-02-01",{"name":541,"class":44},"Stephanie Berg",2,{"id":544,"slug":545,"hasResults":12,"nctId":546,"briefTitle":547,"officialTitle":547,"acronym":4,"eligibilityCriteria":548,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":549,"targetDuration":4,"studyType":22,"phases":550,"briefSummary":551,"conditions":552,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":601,"lastUpdatePostDateStruct":602,"startDateStruct":604,"completionDateStruct":606,"leadSponsor":608,"locationsCount":213},"100446356","phase-1-phase-i-study-of-tumor-treating-fields-ttf-in-combination-with-cabozantinib-or-with-pembrolizumab-and-nab-paclitaxel-in-patients-with-advanced-solid-tumors-involving-the-abdomen-or-thorax-100446356","NCT05092373","Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax","Inclusion Criteria:\n\n* Participants must have pathologically confirmed advanced\u002Fmetastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian\u002Ffallopian, or endometrial\u002Fprimary peritoneal tumors) involving the abdomen or thorax, cannot tolerate standard therapy or have experienced tumor progression on standard therapy.\n* Age: ≥18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Life expectancy \\>3 months.\n* Normal bone marrow function, defined as absolute neutrophil count ≥1,000\u002FµL; platelets ≥75,000\u002FµL; hemoglobin ≥8 g\u002FdL.\n* Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤5 x ULN).\n* Participants with HCC must have a Child Pugh status A, no clinically significant ascites (requiring pharmacological or interventional treatment), and no history (or increased risk) of esophageal\u002Fgastric bleeding, impaired wound healing, perforation or fistula.\n* Serum creatinine clearance ≥50 mL\u002Fmin by the Cockcroft-Gault formula.\n* Measurable disease by RECIST or evaluable disease.\n* Contraception: Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. Male participants must agree to use effective contraception or abstinence while on study.\n* Able to operate the TTF device independently or with the help of a caregiver.\n\nExclusion Criteria:\n\n* Participants must not receive prior anticancer therapy or radiation therapy within 2 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Participants who are already on cabozantinib and have progressive disease are allowed to transition to treatment with tumor treating fields and cabozantinib. Participants in both cohorts who already started treatments as standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel and Pembrolizumab) are allowed to start on protocol within the first 2-3 weeks of treatment initiation. Palliative radiation therapy is allowed.\n* Participants must have recovered to Grade 0-1 toxicity from prior therapy.\n* Active brain metastasis or leptomeningeal disease. Patients with treated brain metastasis must have stable disease, evidenced by brain imaging for at least 4 weeks and the patient must have been off steroids for at least 2 weeks.\n* The patient has cardiac conditions as follows: uncontrolled: hypertension (blood pressure \\[BP\\] \\> 160\u002F100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class II or above), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heart rate \\> 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly).\n* The patient has concurrent severe and\u002For uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).\n* Concurrent malignancies are permitted if (A) they were previously treated, and all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or (C) with agreement from the PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is allowed.\n* The patient is pregnant or breastfeeding.\n* History of hypersensitivity or contraindication to TTF.\n* Implanted pacemaker, defibrillator or other electrical medical devices.\n* The participant has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or the patient has received prior cabozantinib and discontinued therapy due to unacceptable toxicity.\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.\n* The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.\n* CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significant hematemesis or hemoptysis of \\> 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.\n* CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has prothrombin time\u002Finternational normalized ratio (PT\u002FINR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.\n* CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) \\> 450 ms for men or \\> 470 ms for women.\n* CABOZANTINIB COHORT ONLY: The patient requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤ 81 mg\u002Fday), low dose warfarin (≤ 1mg\u002Fday), and prophylactic low molecular weight heparin (LMWH) are permitted.\n* CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel by tumor are excluded.\n* CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.\n* CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication to cabozantinib.\n* ATEZOLIZUMAB-CONTAINING COHORT: Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if their prior anti-PD-1 or anti-PDL1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study. (B) Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are Grade 1 or 0 using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to Grade 1 or 0 and participants who have been off steroid and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 30 days from Cycle 1, Day 1. Participants with prior irAE pneumonitis (\\>= Grade 2) should not be given atezolizumab.\n* ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics.\n* ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior to first dose.\n* ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.\n* ATEZOLIZUMAB-CONTAINING COHORT: Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g. Wegener's Granulomatosis) are excluded from this study.\n* ATEZOLIZUMAB-CONTAINING COHORT: History of\u002For current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.",{"count":20,"type":21},[24],"This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.",[553,554,555,229,556,557,558,559,560,233,114,115,116,117,59,561,562,60,150,563,154,564,565,566,567,568,28,569,570,571,572,573,574,161,575,576,91,577,578,164,579,580,166,581,582,583,584,585,168,586,587,170,588,589,590,172,173,174,591,177,592,593,67,594,595,179,596,597,181,598,183,599,600,185],"Advanced Breast Carcinoma","Advanced Endometrial Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Malignant Abdominal Neoplasm","Advanced Malignant Female Reproductive System Neoplasm","Advanced Malignant Thoracic Neoplasm","Advanced Ovarian Carcinoma","Advanced Primary Peritoneal Carcinoma","Malignant Abdominal Neoplasm","Malignant Solid Neoplasm","Metastatic Fallopian Tube Carcinoma","Metastatic Malignant Abdominal Neoplasm","Metastatic Malignant Female Reproductive System Neoplasm","Metastatic Malignant Thoracic Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Primary Peritoneal Carcinoma","Prognostic Stage III Breast Cancer AJCC v8","Prognostic Stage IIIA Breast Cancer AJCC v8","Prognostic Stage IIIB Breast Cancer AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Prognostic Stage IV Breast Cancer AJCC v8","Stage III Fallopian Tube Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Primary Peritoneal Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Fallopian Tube Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Primary Peritoneal Cancer AJCC v8","Stage IIIA1 Fallopian Tube Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Fallopian Tube Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Fallopian Tube Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Primary Peritoneal Cancer AJCC v8","Stage IIIC Fallopian Tube Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Primary Peritoneal Cancer AJCC v8","Stage IV Fallopian Tube Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Primary Peritoneal Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Fallopian Tube Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Primary Peritoneal Cancer AJCC v8","Stage IVB Fallopian Tube Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Primary Peritoneal Cancer AJCC v8","2026-01-13",{"date":603,"type":37},"2026-01-14",{"date":605,"type":37},"2022-04-29",{"date":607,"type":21},"2026-09-01",{"name":472,"class":44},{"id":610,"slug":611,"hasResults":12,"nctId":612,"briefTitle":613,"officialTitle":613,"acronym":614,"eligibilityCriteria":615,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":616,"targetDuration":4,"studyType":22,"phases":618,"briefSummary":619,"conditions":620,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":622,"lastUpdatePostDateStruct":623,"startDateStruct":624,"completionDateStruct":626,"leadSponsor":628,"locationsCount":629},"100385510","phase-2-a-phase-ii-study-assessing-stereotactic-radiotherapy-in-therapeutic-strategy-of-oligoprogressive-renal-cell-carcinoma-metastases-100385510","NCT04299646","A Phase II Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases","GETUG-StORM-01","Inclusion Criteria:\n\n* Clear cell renal cancer histologically proved (association with other histologic component are permitted)\n* Patients of good or intermediate prognostic, according to Heng criteria\n* Extracerebral metastatic disease documented with imagery\n* Patients treated in first or second line systemic therapy\n* Systemic treatment may be targeted therapies (tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors) and\u002For immunotherapy according to French applicable standards; patients treated in a clinical trial are also eligible if allowed by trial sponsor\n* Oligoprogressive disease documented with imagery, defined as the emergence or progression of 1 to 3 metastases and progression localized in up to 2 organs\n* Oligoprogressive disease confirmed with 2 CT scans performed 2 months apart\n* At least one measurable progressing metastasis according to R.E.C.I.S.T. criteria v1.1\n* All oligoprogressive target lesions measuring ≤ 4 cm\n* Good general condition (WHO performance status ≤ 2)\n* All progressive lesions have to be accessible to SRT, performed concurrently or sequentially\n* No contraindication to systemic therapy and stereotactic radiation therapy\n* Patients aged 18 years or older\n* Signed informed consent form\n* Patients affiliated to the social security system\n\nExclusion Criteria:\n\n* More than 3 progressive metastases\n* Non measurable disease according R.E.C.I.S.T. criteria\n* Patients who received 3 or more lines of systemic therapy\n* Inability to treat all progressive metastatic sites with SRT\n* Previous radiation therapy performed in ≥ 1 target lesion\n* At least 1 oligoprogressive target lesion measuring \\> 4 cm\n* Presence of brain metastases\n* Presence of ultra-central pulmonary metastasis\n* Progressing metastasis in a long bone\n* At least 1 progressive metastasis requiring surgical treatment\n* Current or past history of second neoplasm diagnosed within the last 5 years\n* Pregnancy or breast feeding or inadequate contraceptive measures\n* Patients who cannot be adequately followed up\n* Patient deprived of freedom or under guardianship",{"count":617,"type":21},77,[25],"Every year, 12500 primary renal cell carcinoma (RCC) are diagnosed in France. Metastases occur in half of RCC patients.\n\nManagement of metastatic RCC is based on systemic treatments (targeted therapies\u002Fimmunotherapy). However, resistance to systemic treatment is frequent. In case of progression, usual therapeutic attitude is initiating another systemic therapy.\n\nBecause of the emergence of resistant tumor clonal cells, some patients progress only on few sites while the rest of tumor burden is controlled. In this setting named oligoprogressive disease \\[isolated progression of \\\u003C3-5 metastase(s)\\], ablative treatments of these evolving metastatic sites could allow a disease control and a reduced risk of new metastases occurrence by tumor-cell reembolization. Such strategy is challenging to prolong ongoing systemic treatment and delay further lines.\n\nAlthough RCC was considered radioresistant and radiotherapy with conventional fractionation was mainly used for palliation of symptoms, stereotactic radiotherapy (SRT), by delivering high dose in one or few fractions, allows local control for about 90% of RCC metastases through various radiobiological pathways. Furthermore, some data suggest that high-dose focal irradiation of RCC could induce a systemic antitumor response mediated by immunologic effectors(1). This phenomenon (\"abscopal effect\") could be enhanced in patients under immunotherapy, including anti-PD1.\n\nSeveral retrospective studies and one non-randomized phase-II study highly suggest the interest of SRT as focal ablative treatment in RCC oligometastases with excellent local control rates and low toxicity(2,3).\n\nFurthermore, the multicentric retrospective study the sponsor recently conducted within the GETUG group among 101 metastatic RCC patients with oligoprogression under systemic therapy highlighted that SRT on progressive sites provided a median of 8.6-month progression-free survival and allowed to continue current systemic line for 10.5 months.\n\nHowever, to date, there are no prospective data assessing the interest of SRT for management of oligoprogressive metastatic RCC.\n\nThe sponsor aim to prospectively evaluate the interest of SRT as a therapeutic strategy for local control of oligoprogressive metastatic RCC under ongoing systemic treatment, and consequently delay subsequent systemic treatment.",[28,621],"Radiotherapy","2026-01-12",{"date":601,"type":37},{"date":625,"type":37},"2020-07-01",{"date":627,"type":21},"2029-08",{"name":274,"class":44},30,{"id":631,"slug":632,"hasResults":12,"nctId":633,"briefTitle":634,"officialTitle":635,"acronym":4,"eligibilityCriteria":636,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":637,"targetDuration":4,"studyType":22,"phases":638,"briefSummary":639,"conditions":640,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":643,"lastUpdatePostDateStruct":644,"startDateStruct":646,"completionDateStruct":648,"leadSponsor":650,"locationsCount":213},"100437315","phase-2-trial-of-stereotactic-body-radiation-therapy-sbrt-for-oligoprogression-on-immune-checkpoint-inhibitors-ici-in-metastatic-renal-cell-carcinoma-100437315","NCT04974671","Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma","Phase II Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma","Inclusion Criteria:\n\nIn order to be eligible for participation in this trial, the subject must:\n\n1. Be willing and able to provide written informed consent\u002Fassent for the trial\n2. Be ≥ 18 years of age on day of signing informed consent.\n3. Have histologically confirmed renal cell carcinoma with metastatic disease detected on imaging. Biopsy of metastasis is preferred but not required\n4. The subject has a performance status of 0, 1, or 2 on the ECOG Performance Scale\n5. The life expectancy is \\> 6 months\n6. The most recent systemic therapy must be an ICI-containing regimen, delivered for at least 3 months prior to development of oligoprogressive lesions, with the last dose received within 3 months of trial enrollment.\n7. Oligoprogression - defined as documented progression in up to 5 individual lesions with no previous local therapy to those sites using one of the following criteria:\n\n   7.1 RECIST 1.1 7.1.1 At least a 20% increase in the sum of diameters of target lesions (long axis for non-nodal lesions, short axis for nodal lesions), using the previous imaging as a baseline 7.1.2 The sum of all diameters must demonstrate an absolute increase of at least 5 mm 7.1.3 The appearance of at least one new unequivocal lesion 7.2 PERCIST 7.2.1 SUVpeak, normalized to lean body mass (SUL) increase by at least 30% and increase by at least 0.8 SUL of the target lesion 7.2.2 Development of at least one new lesion 7.2.3 Increase in target lesion size by 30% 7.2.4 Unequivocal progression of nontarget lesions 7.3 Progressive enlargement of a known metastasis on 2 consecutive imaging studies at least 2 months apart with a minimum 5 mm increase in size 7.4 Development of a new soft tissue metastatic lesion at least 5 mm in size or any new bone metastasis\n8. There is no restriction on the total number of metastases\n9. Demonstrate adequate organ function as defined in Table 4, all screening labs should be performed within 28 days of protocol treatment\n\n   Table 4 Adequate Organ Function Laboratory Values\n\n   System Laboratory Value\n\n   Hematological\n\n   Absolute neutrophil count (ANC) ≥ 1,500 \u002FmcL Platelets ≥ 75,000 \u002F mcL Hemoglobin ≥ 9 g\u002FdL\n\n   Renal - IF SBRT will be delivered to a lesion in or abutting the kidney\n\n   Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculated\\* creatinine clearance (GFR can also be used in ≥30 mL\u002Fmin for subject with creatinine place of creatinine or CrCl) levels \\> 1.5 X institutional ULN\n\n   Hepatic - IF SBRT will be delivered to a lesion in or abutting the liver\n\n   Serum total bilirubin ≤ 1.5 X ULN Direct bilirubin Direct bilirubin ≤ ULN for subjects with total bilirubin levels \\> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR\n   * 5 X ULN for subjects with liver metastases\n\n     * Creatinine clearance should be calculated per institutional standard\n10. Able to be treated with SBRT at a Yale radiation oncology facility\n11. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of SBRT. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n12. Female subjects of childbearing must use an effective form of birth control during this study. Acceptable and highly effective birth control methods include intra-uterine hormone releasing system as well as other methods of birth control including consistent use of an approved oral contraceptive (birth control pill), an implantable contraceptive, an injectable contraceptive, a double-barrier method, or true abstinence. Oral, implantable, or injectable contraceptives are only considered effective if used properly and started at least 30 days prior to the screening visit and continue for 120 days after last dose of study drug. (Reference Section 5.7)\n13. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy\n\nExclusion Criteria:\n\nThe subject must be excluded from participating in the trial if the subject\n\n1. Has had radiation therapy within 2 weeks of the first protocol treatment.\n2. Has brain-only oligoprogression. subjects with brain and systemic oligoprogression can still be considered, however treatment of brain metastases will be per standard of care prior to receiving study SBRT.\n3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment. The use of lowdose steroids for management of chronic conditions is allowed (up to 12mg prednisone orally per day or the equivalent).\n4. Has had prior radiation therapy within 2 weeks of the first protocol treatment.\n5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.\n6. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma\u002Fatopy would be an example of an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded. Those with Sjorgen's syndrome will not be excluded from the study.\n7. Has a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or underlying lung disease that according to the treating physician makes the patient ineligible.\n8. Has an active infection requiring systemic therapy.\n9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.\n10. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected).\n11. Has received a live vaccine within 30 days prior to the first protocol treatment.\n12. Has serious medical comorbidities precluding radiotherapy. These include subjects with connective tissue diseases such as lupus or scleroderma, Crohn's disease in subjects where the GI tract will receive radiation\n13. Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed as long as the composite plan meets dose constraints",{"count":629,"type":21},[25],"This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment.",[396,28,641,642],"Oligoprogressive","Progression","2025-12-03",{"date":645,"type":37},"2025-12-04",{"date":647,"type":37},"2023-12-22",{"date":649,"type":21},"2028-04-01",{"name":651,"class":44},"Yale University",{"id":653,"slug":654,"hasResults":12,"nctId":655,"briefTitle":656,"officialTitle":657,"acronym":4,"eligibilityCriteria":658,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":659,"targetDuration":4,"studyType":22,"phases":661,"briefSummary":662,"conditions":663,"keywords":4,"overallStatus":428,"whyStopped":4,"lastUpdateSubmitDate":668,"lastUpdatePostDateStruct":669,"startDateStruct":671,"completionDateStruct":673,"leadSponsor":675,"locationsCount":542},"100609754","phase-2-rp2-and-tivozanib-for-the-treatment-of-metastatic-renal-cell-cancer-after-progression-on-immunotherapy-100609754","NCT07218692","RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy","A Phase 2 Study of RP2 With Tivozanib in Patients With Metastatic Renal Carcinoma After Progression to Immunotherapy","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* Must be willing to consent to provide fresh tumor biopsy sample or archival tumor biopsy sample obtained within 90 days before the first dose of study treatment\n\n  * If unavailable, exceptions may be granted with study principal investigator (PI) approval\n* Male or female who is 18 years of age or older at the time of signed informed consent\n* Eastern Cooperative Oncology Group (ECOG) 0 or 1\n* Histologically confirmed renal cell carcinoma with a clear-cell or sarcomatoid component\n* Patients must have received exactly one prior line or two prior lines of systemic therapy in the advanced or metastatic setting, including mandatory exposure to both an immune checkpoint inhibitor (ICI) and one antiangiogenic tyrosine kinase inhibitor (TKI). Prior treatment with hypoxia inducible factor (HIF)-α inhibitors is not permitted. Patients who received adjuvant immunotherapy and experienced disease recurrence within 6 months of completing treatment may also be eligible, and such therapy will count toward prior lines\n* Has injectable tumor(s), which alone or in aggregate, total at least 1 cm in diameter of RP2\n* Has at least 1 measurable tumor of ≥ 1 cm in longest diameter (or ≥ 1.5 cm shortest diameter for lymph nodes) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy\n* White blood cell (WBC) count ≥ 2.0 x 10\\^9\u002FL\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3\n\n  * NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement\n* Platelets ≥ 100,000\u002Fmm\\^3\n\n  * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement\n* Hemoglobin ≥ 9g\u002FdL\n\n  * NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)\n* Aspartate aminotransferase (AST) ≤ 3.0 x ULN\n* Alanine aminotransferase (ALT) ≤ 3.0 x ULN\n* Creatinine clearance of ≥ 30 mL\u002Fmin per the Cockcroft-Gault formula or serum creatinine \\\u003C 1.5 x upper limit of normal (ULN)\n* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN\n* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants\n* Left ventricular ejection fraction (LVEF) ≥ 50%\n\n  * Note: To be performed within 28 days prior to day 1 of protocol therapy\n* QT interval corrected for heart rate using Bazetts's formula (QTcB) ≤ 480 ms\n\n  * Note: To be performed within 28 days prior to day 1 of protocol therapy\n* Women of childbearing potential (WOCBP) must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU\u002FL or equivalent units of β-hCG within 72 hours before the first dose and a negative urine pregnancy test on dose 1 day 1\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at and for at least (a) 90 days after the last dose of RP2 or for one month after the last dose of tivozanib. Men must also agree to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of RP2\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Received a live vaccine within 28 days before the first dose of study treatment\n\n  * Note: Seasonal influenza vaccines for injection or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are generally inactivated vaccines and are allowed. Live\u002Fattenuated vaccines (such as the intranasal influenza vaccines) are not allowed\n* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment\n\n  * Note: Patients who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent\n* Systemic anticancer therapies within 4 weeks of the first dose of study drug. The prior anti-PD-1 or anti-PD-L1 containing regimen is excluded from this requirement\n* Received prior treatment with an oncolytic virus therapy\n* Received radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities (except for radiation-induced xerostomia), not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease\n\n  * Note: Patients must have recovered (to grade ≤ 1 or baseline) from all adverse events (AEs) due to previous therapies. Patients with grade ≤ 2 neuropathy may be eligible if approved by the medical monitor\n* Unstable cardiac disease as defined by one of the following:\n\n  * Cardiac events such as myocardial infarction (MI) within the past 6 months\n  * NYHA (New York Heart Association) heart failure class III-IV\n  * Uncontrolled atrial fibrillation or hypertension\n* History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment; known hypersensitivity to Chinese hamster ovary cell products\n* Known human immunodeficiency virus (HIV) infection\n* Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \\[HBsAg\\] reactive) or known acute or chronic hepatitis C virus (defined as HCV ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected)\n\n  * Note 1: If HCV RNA testing not available, may use quantitative HCV RNA testing (preferred) or qualitative HCV antibody detection\n  * Note 2: For patients with known acute or chronic hepatitis B virus (HBV) and\u002For HCV infection, HBV and\u002For HCV viral load by real-time polymerase chain reaction (qPCR) must be below the limit of quantitation for the laboratory test used, and they must not have had recent treatment within 12 weeks for HBV or HCV with antiviral medications. Patients with acute or chronic HBV or HCV must be expected to not require antiviral therapy during the RP2 treatment period\n* Clinically significant uncontrolled illness\n* Active significant herpetic infections or prior complications of herpes simplex virus 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or intravenous \\[IV\\]) antivirals with known antiherpetic activity (eg, acyclovir)\n\n  * Note: Patients with sporadic cold sores may be enrolled if no active cold sores are present at the time of dose 1 day 1\n* Systemic infection requiring IV antibiotics or other serious infection within 14 days before dosing\n* Significant bleeding event within the last 12 months that places the patient at unjustifiable risk for bleeding from intratumoral injection procedures, based on Investigator or interventional radiologist assessment\n* Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Known central nervous system (CNS) metastases and\u002For carcinomatous meningitis\n* History of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), non-infectious pneumonitis that required steroids, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan\n\n  * Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Active tuberculosis\n* History or evidence of psychiatric, substance abuse, or any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or the medical monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion\n* Active, known, or suspected autoimmune disease requiring systemic treatment\n\n  * Note: Patients with type 1 diabetes mellitus and\u002For hypothyroidism requiring only hormone replacement, and\u002For with autoimmune skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, and\u002For prior non-serious autoimmune conditions not expected to recur are permitted to enroll\n* Conditions requiring treatment with immunosuppressive doses (\\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids within 14 days before dose 1 day 1\n\n  * Note: Patients who require a brief course (≤ 7 days) of corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg\u002Fday prednisone equivalent\n* History of life-threatening toxicity related to prior immune therapy (eg, anti-cytotoxic T lymphocyte antigen 4 or anti-PD-1\u002Fanti-PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways \\[eg, CD40,4-1BB\\]) except those that are unlikely to recur or are expected to be manageable with standard countermeasures (eg, hormone replacement after adrenal crisis). Individual cases should be discussed with medical monitor if needed\n* Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on coumadin with a target INR \\> 2.5 or that cannot be temporarily reversed to INR ≤ 1.7\n* Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks before treatment\n* Prior organ transplantation including allogeneic stem-cell transplantation\n* Major surgery within 28 days before starting treatment or anticipated major surgery while on study\n\n  * Note: If a patient received major surgery, they must have recovered adequately from the intervention before starting study treatment and must have adequate wound healing, based on investigator's assessment or surgeon's assessment, before starting tivozanib\n* Females only: Pregnant or breastfeeding\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":660,"type":21},35,[25],"This phase II trial tests the effect of RP2 and tivozanib in treating patients with renal cell cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that is growing, spreading, or getting worse (progressive) after receiving immunotherapy with immune checkpoint inhibitors (ICIs). RP2 is a herpes simplex virus (a viral infection commonly known as the \"cold sore virus\") that has been changed to infect and destroy tumor cells and to activate (turn on) the human immune system to attack the tumor cells. Tivozanib hydrochloride blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Tivozanib hydrochloride is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Giving RP2 and tivozanib may be safe, tolerable, and\u002For effective in treating patients with metastatic renal cell cancer that has progressed after receiving immunotherapy with ICIs.",[529,233,664,665,28,666,667,91,67],"Advanced Sarcomatoid Renal Cell Carcinoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Sarcomatoid Renal Cell Carcinoma","Recurrent Renal Cell Carcinoma","2025-10-16",{"date":670,"type":37},"2025-10-20",{"date":672,"type":21},"2026-08-11",{"date":674,"type":21},"2027-08-11",{"name":676,"class":44},"City of Hope Medical Center",{"id":678,"slug":679,"hasResults":12,"nctId":680,"briefTitle":681,"officialTitle":682,"acronym":683,"eligibilityCriteria":684,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":685,"targetDuration":4,"studyType":22,"phases":687,"briefSummary":688,"conditions":689,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":690,"lastUpdatePostDateStruct":691,"startDateStruct":693,"completionDateStruct":695,"leadSponsor":697,"locationsCount":700},"100401695","phase-3-comparing-the-outcome-of-immunotherapy-based-drug-combination-therapy-with-or-without-surgery-to-remove-the-kidney-in-metastatic-kidney-cancer-the-probe-trial-100401695","NCT04510597","Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial","Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)","PROBE","Inclusion Criteria:\n\n* STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible\n* STEP 1 REGISTRATION: Participants must have primary tumor in place\n* STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:\n\n  * Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)\n  * CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast\n\nScans must be performed within the following timeframes:\n\n* Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration\n* Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment\n\n  * STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration\n  * STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy\n  * STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System\n  * STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines\n  * STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system\n  * STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+\u002F- 2 weeks) after starting pre-randomization treatment\n* CT scan of the chest (can be performed without contrast if CT contrast cannot be given)\n* CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2\n\n  • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment\n* Stable disease\n* Partial response\n* The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1\n\n  * STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment\n  * STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy\n  * STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:\n* 2 infusions of nivolumab + 1 infusion of ipilimumab\n* 2 infusions of pembrolizumab\n* 2 infusions of avelumab\n\n  * STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization\n  * STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization\n  * STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization\n  * STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization\n  * STEP 2 REGISTRATION: Total bilirubin =\\\u003C institutional upper limit of normal (ULN) (within 28 days prior to randomization)\n  * STEP 2 REGISTRATION: Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)\n  * STEP 2 REGISTRATION: Serum creatinine =\\\u003C 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance \\>= 50 mL\u002Fmin using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)\n\nExclusion Criteria:\n\n* STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease\n* STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:\n\n  * Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy\n  * Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment\n* STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:\n\n  * Treatment naive participants must not have received any pre-randomization treatment.\n  * Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:\n\n    * 4 infusions of nivolumab\n    * 4 infusions of ipilimumab\n    * 4 infusions of pembrolizumab\n    * 7 infusions of avelumab\n* STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:\n\n  * Treatment naive participants must not have received any immunotherapy within a year of registration\n  * Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment\n* STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney\n* STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years\n* STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy\n* STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed\n* STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease\n* STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years",{"count":686,"type":21},364,[56],"This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.",[665,28,67],"2025-09-02",{"date":692,"type":37},"2025-09-09",{"date":694,"type":37},"2021-03-08",{"date":696,"type":21},"2033-07",{"name":698,"class":699},"SWOG Cancer Research Network","NETWORK",387,{"id":702,"slug":703,"hasResults":12,"nctId":704,"briefTitle":705,"officialTitle":706,"acronym":707,"eligibilityCriteria":708,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":709,"enrollmentInfo":710,"targetDuration":4,"studyType":22,"phases":711,"briefSummary":712,"conditions":713,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":723,"lastUpdatePostDateStruct":724,"startDateStruct":726,"completionDateStruct":728,"leadSponsor":730,"locationsCount":213},"100500493","phase-3-measuring-oncological-value-of-exercise-and-statin-100500493","NCT05796973","Measuring Oncological Value of Exercise and Statin","Syöpäpotilaan Ennusteen Parantaminen Muuttamalla syövän mikroympäristöä ja Metaboliaa Liikunnalla ja lääkkeellisesti - Measuring Oncological Value of Exercise and Statin","MOVES","Inclusion Criteria:\n\n* The patient has metastatic prostate cancer, breast cancer, ovarian cancer or kidney cancer confirmed histologically and by imaging, for which 1st-line cancer drug treatment is started\n* Prostate cancer: First course of docetaxel treatment or second-generation antiandrogen treatment for metastatic prostate cancer.\n* Breast cancer: First-line medical treatment of metastatic breast cancer regardless of hormone receptor status.\n* Kidney cancer: Kidney cancer, for which 1st-line cancer drug treatment is started as tki monotherapy and\u002For IO monotherapy or as a combination therapy.\n* Ovarian cancer: stage III or IV cancer for which chemotherapy treatment is started.\n* The patient agrees to the study and signs a written informed consent.\n* Adult (18 years=\\>) women (breast, ovarian and kidney cancer) and men (prostate and kidney cancer) are recruited for the study.\n* In women, the use of a reliable contraceptive during the intervention\n\nExclusion Criteria:\n\n* High risk of bone fractures\n* Inability to physical exertion and\u002For unsuitability for cancer drug treatment\n* Poor co-operation ability for psychological reasons\n* Active use of cholesterol-lowering drugs\n* Severe liver or kidney failure\n* Troublesome side effects that occurred in the past during cholesterol medication\n* Continuous use of medicinal substances that interact with atorvastatin during the study period\n* A special group of subjects according to the EU Clinical Trials Regulation 536\u002F2014 (e.g. pregnant or lactating women)\n\nExclusion criteria in patients who are already using statin medication before the study:\n\n* High risk of bone fractures\n* Inability to physical exertion and\u002For unsuitability for cancer drug treatment\n* Poor co-operation ability for psychological reasons\n* Severe liver or kidney failure\n* A special group of subjects according to the EU Clinical Trials Regulation 536\u002F2014 (e.g. pregnant or lactating women)","99 Years",{"count":87,"type":21},[56],"The aim of the study is to find out whether supervised physical exercise during cancer drug treatment improves the effectiveness of the treatment in metastasized breast, kidney, ovarian and prostate cancer compared to unsupervised exercise. In addition, the investigators are investigating whether the use of atorvastatin combined with guided group exercise training would further improve the response to cancer treatment.",[714,715,397,716,717,718,28,528,719,720,721,722],"Prostate Cancer","Breast Cancer","Ovarian Cancer","Metastatic Breast Cancer","Metastatic Kidney Cancer","Metastatic Prostate Cancer","Metastatic Prostate Adenocarcinoma","Metastatic Ovarian Cancer","Metastatic Ovary Cancer","2025-06-23",{"date":725,"type":37},"2025-06-27",{"date":727,"type":37},"2023-03-31",{"date":729,"type":21},"2027-12-31",{"name":731,"class":44},"Tampere University Hospital",{"id":733,"slug":734,"hasResults":12,"nctId":735,"briefTitle":736,"officialTitle":737,"acronym":4,"eligibilityCriteria":738,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":739,"targetDuration":4,"studyType":22,"phases":740,"briefSummary":741,"conditions":742,"keywords":746,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":751,"lastUpdatePostDateStruct":752,"startDateStruct":754,"completionDateStruct":756,"leadSponsor":758,"locationsCount":760},"100497644","phase-1-first-in-human-phase-i-study-to-evaluate-safety-tolerability-and-antineoplastic-activity-of-oatd-02-in-patients-with-selected-advanced-andor-metastatic-solid-tumours-100497644","NCT05759923","First-in-human Phase I Study to Evaluate Safety, Tolerability and Antineoplastic Activity of OATD-02 in Patients with Selected Advanced And\u002For Metastatic Solid Tumours","An Open-label, Multicentre, Dose-escalation, First-in-human Phase I Study to Evaluate Safety, Tolerability and Antineoplastic Activity of OATD-02 in Patients with Selected Advanced And\u002For Metastatic Solid Tumours (colorectal Cancer, Ovarian Cancer, Pancreatic Cancer or Renal Cell Carcinoma)","Inclusion Criteria:\n\n1. Capable of understanding and complying with protocol requirements.\n2. Male or female patient aged ≥18 years at Screening.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n4. Histologically or cytologically confirmed advanced and\u002For metastatic colorectal cancer, renal cell cancer, or pancreatic cancer or recurrent serous ovarian cancer (platinum-resistant\u002Fineligible to receive platinum-based chemotherapy), that either progressed or relapsed after all relevant standard of care cancer therapies (at least 1 line of systemic cancer therapy).\n5. Written informed consent given by the patient before the initiation of any study procedures.\n\nExclusion Criteria:\n\n1. Unable to take oral medications.\n2. Clinically active central nervous system metastases and\u002For carcinomatous meningitis.\n3. Major surgery within 30 days before the first IMP dose.\n4. Pregnant or breastfeeding women.\n5. Known allergy to excipients of the IMP.\n6. Severe, uncontrolled systemic disease which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to participate in the study.\n7. Participation in another clinical study within 4 weeks before the first IMP dose.",{"count":446,"type":21},[24],"The goal of this clinical trial is to learn if the OATD-02 administration (orally) in monotherapy is safe and has the pharmacodynamic potential to restore and enhance tumour responses to immunotherapy through increased arginine levels or intrinsic anti-tumour activity in participants with advanced metastatic colorectal cancer, ovarian cancer, renal cancer or pancreatic cancer.",[559,233,743,744,745,452,28,567],"Advanced Pancreatic Carcinoma","Advanced Colorectal Carcinoma","Metastatic Pancreatic Carcinoma",[747,301,748,749,750],"solid tumors","ovarian cancer","pancreatic cancer","colorectal cancer","2025-02-20",{"date":753,"type":37},"2025-02-24",{"date":755,"type":37},"2023-01-26",{"date":757,"type":21},"2025-12",{"name":759,"class":311},"Molecure S.A.",3,{"id":762,"slug":763,"hasResults":12,"nctId":764,"briefTitle":765,"officialTitle":766,"acronym":767,"eligibilityCriteria":768,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":769,"targetDuration":4,"studyType":771,"phases":4,"briefSummary":772,"conditions":773,"keywords":774,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":778,"lastUpdatePostDateStruct":779,"startDateStruct":781,"completionDateStruct":783,"leadSponsor":785,"locationsCount":213},"100558265","retrospective-analysis-of-patients-with-metastatic-renal-cell-carcinoma-treated-with-cabozantinib-100558265","NCT06548867","Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib","Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib: a GENomic Signature for Describing Long-lasting Response","CABOGEN","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Patients with histological diagnosis of predominantly clear cell carcinoma\n* Availability of the tumor tissue from the primary tumor and\u002For a metastatic site for the genomic profiling analysis not older than 5 years.\n* Evaluable disease according to RECIST criteria v 1.1\n* Treatment with cabozantinib after one or more previous therapies for mRCC\n* Patient progressed from the start to cabozantinib therapy within 3 months or after 9 months\n* Any prognosis group according to the IMDC risk score\n* Signed informed consent must be obtained for living patients. Patients who died and patient untraceable will be analyzed based on the Authorization no. 9\u002F2016 of the Italian Data Protector Supervisor.\n\nExclusion Criteria:\n\n* Non-availability of tumor tissue from the primary tumor or a metastatic site for biomarker analysis\n* Patient progressed between 3 and 9 months from the beginning of treatment with cabozantinib.\n* Non-availability of clinical information useful to evaluate the IMDC risk group at baseline.",{"count":770,"type":21},80,"OBSERVATIONAL","CABOGEN is a Observational, retrospective, multicenter study that will enroll patients with metastatic clear cell renal carcinoma (mccRCC) treated with cabozantinib after one or more previous lines of treatment that included TKIs, immune checkpoint inhibitors or mTOR inhibitors.",[28],[28,775,776,777],"Genomic signature","long lasting response","cabozantinib treatment","2024-08-08",{"date":780,"type":37},"2024-08-12",{"date":782,"type":37},"2024-05-28",{"date":784,"type":21},"2025-06-30",{"name":786,"class":44},"Gruppo Oncologico Italiano di Ricerca Clinica",{"id":788,"slug":789,"hasResults":12,"nctId":790,"briefTitle":791,"officialTitle":792,"acronym":4,"eligibilityCriteria":793,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":794,"targetDuration":4,"studyType":22,"phases":796,"briefSummary":797,"conditions":798,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":782,"lastUpdatePostDateStruct":799,"startDateStruct":801,"completionDateStruct":803,"leadSponsor":805,"locationsCount":213},"100546781","phase-1-cbm588-capsules-in-combination-with-nivolumab-and-ipilimumab-for-the-treatment-of-advanced-stage-kidney-cancer-100546781","NCT06399419","CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer","An Open-Label, Phase I, Dose-Finding Study of CBM588 in Combination With Nivolumab\u002FIpilimumab for Patients With Advanced Stage Renal Cell Carcinoma","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* Agreement to allow the use of archival tissue from diagnostic tumor biopsies\n\n  * If unavailable, exceptions may be granted with study principle investigator (PI) approval\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Age ≥ 18 years\n* Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component or sarcomatoid component\n* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \\[AJCC\\] stage IV) renal cell carcinoma with intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria\n* No prior systemic therapy for renal cell carcinoma (RCC) with the following exception:\n\n  * One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy\n* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy\n* Absolute neutrophil count (ANC) ≥ 1500\u002FuL without granulocyte colony-stimulating factor support\n* White blood cell count ≥ 2500\u002FuL\n* Platelets ≥ 100,000\u002FuL without transfusion\n* Hemoglobin ≥ 8 g\u002FdL\n* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases\n* Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)\n* Serum albumin ≥ 2.8 g\u002Fdl\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) or partial thromboplastin time (PTT) test \\\u003C 1.3 x the laboratory ULN\n* Serum calculated creatinine clearance ≥ 50mL\u002Fmin using the Cockcroft-Gault equation\n* Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab for women with childbearing potential, and 7 months after the last dose of nivolumab for men\n* Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \\\u003C 55 years-of-age must have a serum follicle stimulating (FSH) level \\> 40 mIU\u002FmL to confirm menopause).\n\n  * Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site\n\nExclusion Criteria:\n\n* Prior treatment with ipilimumab and\u002For nivolumab\n* Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent\n* Active interstitial lung disease (ILD)\u002Fpneumonitis or history of ILD\u002Fpneumonitis requiring treatment with systemic steroids\n* Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results\n* Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment\n* Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible\n* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment\n* Administration of a live, attenuated vaccine within 30 days before first dose of study treatment\n* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Any condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed\n  * Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection\n  * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan\n  * Malabsorption syndrome\n  * Uncompensated\u002Fsymptomatic hypothyroidism\n  * Moderate to severe hepatic impairment (Child-Pugh B or C)\n  * Requirement for hemodialysis or peritoneal dialysis\n  * History of solid organ or allogenic stem cell transplant\n  * Other clinically significant disorders that would preclude safe study participation\n\n    * Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions:\n\n      * Type 1 diabetes mellitus\n      * Hypothyroidism only requiring hormone replacement\n      * Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment\n      * Conditions not expected to recur in the absence of an external trigger\n* Pregnant or lactating females\n* Inability to swallow tablets\u002Fcapsules or unwillingness or inability to receive IV administration\n* Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded\n* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast\n* Exclusion of subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry\n* Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":795,"type":21},28,[24],"This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588 in combination with nivolumab and ipilimumab in treating patients with kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). CBM588 is a live biotherapeutic that may help improve the effects of immunotherapy. Nivolumab and ipilimumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread by enhancing the ability of the body's immune cells to attack tumor cells. CBM588 in combination with nivolumab and ipilimumab may be safe, tolerable, and\u002For effective in treating patients with advanced stage kidney cancer.",[529,233,664,665,28,666,91,67],{"date":800,"type":37},"2024-05-30",{"date":802,"type":21},"2024-06-19",{"date":804,"type":21},"2026-10-19",{"name":806,"class":311},"Osel, Inc."]