[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"clear-cell-renal-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:clear-cell-renal-carcinoma":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,40],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":17,"targetDuration":4,"studyType":20,"phases":21,"briefSummary":23,"conditions":24,"keywords":4,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":28,"lastUpdatePostDateStruct":29,"startDateStruct":32,"completionDateStruct":34,"leadSponsor":36,"locationsCount":39},"100588370","phase-2-phase-ii-trial-of-ivonescimab-in-previously-treated-patients-with-advanced-clear-cell-renal-cell-carcinoma-100588370",false,"NCT06940518","Phase II Trial of Ivonescimab in Previously Treated Patients With Advanced Clear Cell Renal Cell Carcinoma","Inclusion Criteria\n\n1. Participants with histologically or cytologically confirmed metastatic\u002Fadvanced clear cell RCC with a clear cell component who have received at least one prior line of systemic treatment in the advanced or metastatic setting, including a PD-1\u002FPD-L1 checkpoint inhibitor administered in metastatic\u002Fadvanced setting.\n\n   1. Participants in cohort 1 must have not received a treatment containing a VEGF- or HIF2a(- directed agent in prior treatment lines of treatment for metastatic\u002Fadvanced RCC\n   2. Participants in cohort 2 must have had progression on or after at least one prior line of treatment containing a VEGF-directed agent in prior lines of therapy\n2. Participants must have had evidence of disease progression on or after last treatment regimen received.\n3. Participants who received HIF-2ƒ¿ inhibitors in prior lines of therapy are eligible in cohort 2 but not cohort 1.\n4. Participants who received adjuvant immune checkpoint inhibitor are eligible, provided that they had progression while on adjuvant therapy, in which case they would be enrolled in cohort 1. Participants who recur after completing adjuvant therapy should receive a PD-1\u002FPD-L1 checkpoint inhibitor in the advanced\u002Fmetastatic setting to be eligible.\n5. Participants must have at least one measurable site of disease per RECIST version 1.1. This is defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). For non-lymph node tumor lesions, they must be a minimum size of ≥ 10 mm. For malignant lymph node lesions, they must be at least ≥ 15 mm in short axis with conventional techniques or ≥10 mm with more sensitive techniques such as MRI or spiral CT scan. If the participant has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.\n6. ECOG performance status ≤2\n7. Age ≥ 18 years\n8. Participants must have adequate organ and marrow function prior to study entry as defined below:\n9. INR and PT ≤ 1.5 x ULN and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 ULN (unless abnormalities are unrelated to coagulopathy). Therapeutic anticoagulation is permitted if: on a stable dose of low molecular weight heparin (LMWH) for \\> 2 weeks (14 days) at the time of enrollment or on a direct oral anticoagulant (DOAC) for \\> 2 weeks at time of enrollment.\n10. Participants 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. To be eligible for this trial, participants should be class 2B or better.\n11. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n12. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Patients who are Hepatitis C virus antibody positive (HCV Ab\n\n    +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.\n13. Participants with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy.\n14. The effects of Ivonescimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men 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. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy\n\n    \\# CLN1114). This includes all female participants , between the onset of menses (as early as 8years of age) and 55 years unless the participants presents with an applicable exclusionary factor which may be one of the following: i. Postmenopausal (no menses in greater than or equal to 12 consecutive months). ii. History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). iv. History of bilateral tubal ligation or another surgical sterilization procedure.\n15. Female participants of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of HCG) before study entry. Pregnancy test must be repeated on the day of first infusion, if test performed \\> 14 days before starting study drug.\n16. Female participants of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab. Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab.\n\n    1. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject\u002FPartner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n\n       * Ability to understand and the willingness to sign a written informed consent document for this clinical trial and the companion Trials LAB02-152 and PA17-0577\n\nExclusion Criteria:\n\n1. Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or postradiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, ductal carcinoma in situ of the breast or low-risk early stage prostate adenocarcinoma with negligible risk of metastasis or death.\n2. Major surgical procedures or serious trauma within 4 weeks prior to enrollment, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment.\n3. Current hypertension with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after adequate oral antihypertensive therapy.\n4. History of bleeding tendencies or coagulopathy and\u002For clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to:\n\n   o Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots).\n\n   Transient hemoptysis associated with diagnostic bronchoscopy is allowed.\n   * Nasal bleeding \u002Fepistaxis. Bloody nasal discharge is allowed.\n   * Hematuria associated with urinary obstruction. Microhematuria or macrohematuria not associated with urinary obstruction are allowed.\n   * Radiologically documented evidence of major blood vessel encasement with narrowing of the vessel that the investigator determines will pose a significantly increased risk of bleeding.\n5. History of major diseases prior to enrollment, specifically:\n\n   * Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \\[NYHA\\] classification . grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)\n   * History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to enrollment.\n6. History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment.\n\n   * Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to enrollment.\n   * History of perforation of the gastrointestinal tract and\u002For fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment.\n7. Symptomatic CNS metastases, leptomeningeal disease, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrolmment, or potential need for CNS radiation within the first cycle of ivonescimab.\n\n   o Participants with treated\u002Fstable brain metastases are allowed on protocol if they had brain metastases that received CNS-directed therapy, such as surgery or treatment with radiosurgery or Gamma knife, without recurrence or edema for at least 1 month (4 weeks). Participants actively requiring glucocorticoids for uncontrolled brain or leptomeningeal metastases are not eligible. Participants must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone . 10 mg daily or equivalent).\n8. Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic inflammatory diarrhea).\n9. Participants who are receiving any other investigational agents.\n10. Active autoimmune disease requiring systemic therapy (e.g., with disease modifying drugs, prednisone \\>10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment. However the following will be allowed:\n\n    * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.\n    * Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted.\n11. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.\n12. Severe infection within 4 weeks prior to enrollment, including but not limited to comorbidities requiring hospitalization, severe sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to enrollment (excluding antiviral therapy for hepatitis B or C).\n13. Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic. Participants managed with indwelling catheters (e.g., PleurX) are allowed.\n14. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivonescimab or other agents used in study. This includes known history of severe hypersensitivity to other monoclonal antibodies.\n15. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n16. Participants with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrollment. All patients with active hepatitis C (hepatitis C virus \\[HCV\\] antibody positive with HCV RNA levels above the lower limit of detection) are excluded.\n17. Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 5.0.\n18. Pregnant women are excluded from this study because ivonescimab is a bispecific agent 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 ivonescimab, breastfeeding should be discontinued if the mother is treated with ivonescimab.\n\n    These potential risks may also apply to other agents used in this study.\n19. Participant is breastfeeding or plans to breastfeed during the study.\n20. Participants with persistent grade ≥ 2 adverse events per NCI CTCAE v5.0 from prior systemic therapies that would confound timely detection of immune-related adverse events due to ivonescimab or otherwise hinder patient participation in the clinical trial.\n21. History or current evidence of any condition (medical \\[including adverse events from prior anticancer therapy, disorders secondary to tumor\\], surgical or psychiatric \\[including substance abuse\\]), or laboratory abnormality that might confound the results of the study, interfere with the participants participation for the full duration of the study, might lead to higher medical risk and\u002For is not in the best interest of the patient to participate, in the opinion of the treating investigator","ALL","18 Years",{"count":18,"type":19},40,"ESTIMATED","INTERVENTIONAL",[22],"PHASE2","To learn if ivonescimab can help to control previously treated, locally advanced or metastatic ccRCC.",[25,26],"Ivonescimab","Clear Cell Renal Carcinoma","RECRUITING","2026-05-13",{"date":30,"type":31},"2026-05-15","ACTUAL",{"date":33,"type":31},"2025-07-02",{"date":35,"type":19},"2030-01-19",{"name":37,"class":38},"M.D. Anderson Cancer Center","OTHER",1,{"id":41,"slug":42,"hasResults":11,"nctId":43,"briefTitle":44,"officialTitle":45,"acronym":46,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":48,"targetDuration":4,"studyType":20,"phases":50,"briefSummary":51,"conditions":52,"keywords":4,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":39},"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":49,"type":19},20,[22],"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.",[53,26,54,55,56,57,58,59,60,61],"Clear Cell Renal Cell Cancer (ccRCC)","Clear Cell Renal Cell Carcinoma Metastatic","Clear Cell Renal Cancer","Bone Metastases of a Malignant Tumor","Clear Cell Renal Cell Carcinoma","Bone, Metastatic Cancer","Metastatic Cancer","Metastatic Renal Cell Carcinoma","Metastases to Bone","NOT_YET_RECRUITING","2026-04-27",{"date":65,"type":31},"2026-05-01",{"date":67,"type":19},"2026-05-30",{"date":69,"type":19},"2030-02-28",{"name":71,"class":38},"Kelly Fitzgerald, MD"]