[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"clinical-stage-iv-cutaneous-melanoma-ajcc-v8\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:clinical-stage-iv-cutaneous-melanoma-ajcc-v8":34},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,16,0,[8,49,96,214,235,260,283,322,344,392,423,443,475,514,525,548],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100053929","phase-1-intralesional-influenza-vaccine-for-the-treatment-of-stage-i-iv-melanoma-100053929",false,"NCT04697576","Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma","Intralesional Influenza Vaccine for Patients With Melanoma","Inclusion Criteria:\n\n* Males or females\n* 18 to 99 years of age\n* Histologically confirmed cutaneous melanoma by historical pathology report review, clinical Stage I-III (Cohort #1), or Stage IV (Cohort #2) cutaneous melanoma\n* At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring ≥ 1 cm by digital caliper (with digital photography documentation) or ultrasound (with ultrasound image documentation)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1\n* Absolute neutrophil count (ANC) \\>= 1.5 x 10\\^3\u002Fmm\\^3 (drawn at or not more than 30 days prior to the screening visit)\n* Hemoglobin (Hgb) \\>= 8 g\u002FdL (drawn at or not more than 30 days prior to the screening visit)\n* Platelet count \\>= 100 x 10\\^3\u002Fmm\\^3 (drawn at or not more than 30 days prior to the screening visit)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 2.5 x upper limit of normal (ULN) or =\\\u003C 5 x ULN in patients with liver metastases (Cohort 2 only) (drawn at or not more than 30 days prior to the screening visit)\n* Prothrombin time =\\\u003C 1.5 x ULN (drawn at or not more than 30 days prior to the screening visit)\n* Total bilirubin =\\\u003C 1.5 x ULN (unconjugated bilirubin of \\\u003C 3 x ULN for patients with known Gilbert syndrome) (drawn at or not more than 30 days prior to the screening visit)\n* Creatinine clearance of \\>= 50 ml\u002Fmin by Cockcroft-Gault equation (drawn at or not more than 30 days prior to the screening visit)\n* Women of childbearing potential (WOCBP) must agree to use effective contraceptive methods from screening until at least:\n\n  * Cohort 1: 14 days after the surgical resection for subjects in Cohort 1\n  * Cohort 2:\n\n    * Nivolumab: 5 months after the last dose of either nivolumab or intralesional Flucelvax, whichever is later\n    * Pembrolizumab: 4 months after the last dose of either pembrolizumab or intralesional Flucelvax, whichever is later\n    * Ipilimumab: 3 months after the last dose of either ipilimumab or intralesional Flucelvax, whichever is later\n    * Relatlimab + nivolumab (marketed under the trade name Opdualag): 5 months after the last dose of either Opdualag or intralesional Flucelvax, whichever is later.\n    * Combination ipilimumab with other checkpoint inhibitor: Whichever is later:\n\n      * 3 months after the last dose of either ipilimumab or intralesional Flucelvax\n      * Above-bulleted recommendation for nivolumab or pembrolizumab\n* Non-childbearing potential is defined as a woman who meets either of the following criteria: a) postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\n* Effective contraception methods are defined as one of the following:\n\n  * True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject\n  * Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception\n  * Condoms and spermicide\n  * Diaphragm and spermicide\n  * Oral or implanted hormonal contraceptive\n  * An intra-uterine device\n* WOCBP must have a negative pregnancy test (serum or urine)\n\nExclusion Criteria:\n\n* Known allergy or intolerance to influenza vaccination\n* Subjects with condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone\u002Fequivalent) or other immunosuppressive medications within 14 days of study drug administration\n* Active, known or suspected autoimmune disease\n* Active brain metastasis or leptomeningeal metastasis\n* Diagnostic biopsy of ocular or mucosal melanoma\n* Any melanoma therapy within 6 months of enrollment; though prior surgical resection is permitted\n* Incarcerated patients\n* Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to randomization: stable and adequate CD4 counts (≥ 350 mm\\^3), and serum HIV viral load of \\\u003C 25,000 IU\u002Fml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria\n* Pregnant or lactating patients\n* Patients incapable of independently providing consent","ALL","18 Years","99 Years",{"count":20,"type":21},36,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This phase I trial investigates the effects of influenza vaccine in treating patients with stage I-IV melanoma. While intramuscular administration of influenza vaccine provides immunization against the influenza virus, giving influenza vaccine directly into the tumor (intralesional) may decrease the size of the injected melanoma tumor, or the extent of the melanoma within the body.",[27,28,29,30,31,32,33,34,35],"Clinical Stage I Cutaneous Melanoma AJCC v8","Clinical Stage IA Cutaneous Melanoma AJCC v8","Clinical Stage IB Cutaneous Melanoma AJCC v8","Clinical Stage II Cutaneous Melanoma AJCC v8","Clinical Stage IIA Cutaneous Melanoma AJCC v8","Clinical Stage IIB Cutaneous Melanoma AJCC v8","Clinical Stage IIC Cutaneous Melanoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Metastatic Melanoma","RECRUITING","2026-07-09",{"date":39,"type":40},"2026-07-13","ACTUAL",{"date":42,"type":40},"2021-10-20",{"date":44,"type":21},"2027-12-31",{"name":46,"class":47},"Carlo Contreras","OTHER",1,{"id":50,"slug":51,"hasResults":11,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":4,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":56,"targetDuration":4,"studyType":22,"phases":58,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":85,"lastUpdatePostDateStruct":86,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":95},"100449723","phase-2-bicazo-a-study-combining-two-immunotherapies-cabozantinib-and-nivolumab-to-treat-patients-with-advanced-melanoma-or-squamous-cell-head-and-neck-cancer-an-immunomatch-pilot-study-100449723","NCT05136196","BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study","Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study","Inclusion Criteria:\n\n* STEP 1 - SPECIMEN SUBMISSION\n* Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible\n\n  * Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration\n* Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration\n* Participants must have had documented progression during or within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and are considered unresectable\n* Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration\n* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration\n* Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration\n* Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)\n* Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management\n* Participants must have recovered to baseline or =\\\u003C grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy\n* Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:\n\n  * If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration\n  * Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration\n  * Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation\n* Participants must not have received prior treatment with anti-VEGF therapies for any reason\n* Participants must be \\>= 18 years of age\n* Participants must have a Zubrod Performance Status 0 or 1\n* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial\n* Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab\u002Fcabozantinib treatment\n* Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules\n* Participants must not have malabsorption syndrome\n* Participants must not have active autoimmune disease requiring systemic steroids (equivalent of \\> 10mg of prednisone) or other immune suppression. Exceptions:\n\n  * Type 1 diabetes mellitus\n  * Endocrinopathy 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* Participants must not have received an organ allograft\n* Participants must not have a history of hemoptysis (defined as \\>= 1\u002F2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration\n* Participants must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with cabozantinib therapy:\n\n  * Prior carotid bleeding\n  * Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies\n  * Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies\n  * Any prior history of bleeding related to the current head and neck cancer\n  * History of gross hemoptysis (bright red blood of 1\u002F2 teaspoon or more per episode of coughing) within 3 months\n* Participants must not require 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)\n\n  * Participants must not require anticoagulants except for 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 participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor\n* Participants must not have evidence of preexisting uncontrolled hypertension 28 days prior to step 1 registration as documented by baseline blood pressure reading with systolic blood pressure \\> 150 mmHg and\u002For diastolic blood pressure \\> 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible\n* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of \"reproductive potential\". In addition to routine contraceptive methods, \"effective contraception\" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation\u002Focclusion and vasectomy with testing showing no sperm in the semen\n* Have an adequate archival tissue specimen verified by the local pathologist and documented on the Pathology Review Form from a procedure obtained after the development of resistance to anti-PD-1\u002FL1 therapy. Archival tissue must consist of tumor block or at least 1 hematoxylin and eosin (H\\&E)-stained 4-5 micron slide and 20 freshly cut serially sectioned and numbered 4-5 micron unstained, uncharged slides OR\n\nBe willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:\n\n* Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial\n* Acceptable biopsy procedures are:\n\n  * Percutaneous biopsy with local anesthetic and\u002For sedation with an expected risk of severe complications \\\u003C 2%\n  * Direct transoral biopsy (with or without local anesthetic and\u002For sedation) with an expected risk of severe complications \\\u003C 2%\n  * Excisional cutaneous biopsy with local anesthetic and\u002For sedation with an expected risk of severe complications \\\u003C 2%\n  * Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol\n  * Removal of additional tumor tissue during a medically necessary surgical procedure\n\n    * Participants must submit whole blood for germline genomic analysis\n    * Participants must have been offered the opportunity to participate in specimen banking\n    * Note: As a 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* 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* Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)\n\n  * STEP 2 TREATMENT REGISTRATION\n* Note: No tests or exams are required to be repeated for step 2 registration (Treatment). However, participants who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration\n\n  * Participants must continue to meet eligibility for step 1 registration prior to step 2 registration\n  * Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration\n  * Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)\n  * Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors \\[RECIST\\] 1.1)\n  * For melanoma participants, CT chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., MR brain, CT abdomen\u002Fpelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician\n  * Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy\n  * Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab\u002Fcabozantinib treatment\n  * Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration\n  * Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration \\[FDA\\] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration\n  * Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 2 registration\n  * Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based coronavirus disease 2019 (COVID-19) vaccine within 30 days prior to step 2 registration\n  * Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration\n  * Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration\n  * Participants must have a history and physical examination performed within 28 days prior to step 2 registration\n  * Leukocytes \\>= 3,000\u002FuL (within 28 days prior to step 2 registration)\n  * Absolute neutrophil count \\>= 1,500\u002FuL (within 28 days prior to step 2 registration)\n  * Platelets \\>= 100,000\u002FuL (within 28 days prior to step 2 registration)\n  * Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) or =\\\u003C 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)\n  * Aspartate aminotransferase (AST) =\\\u003C 3 x institutional ULN (within 28 days prior to step 2 registration)\n  * Alanine aminotransferase (ALT) =\\\u003C 3 x institutional ULN (within 28 days prior to step 2 registration)\n  * Urinalysis: For baseline value (no required value for eligibility)\n  * Measured (OR calculated) creatinine clearance \\>= 30 mL\u002Fmin using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 registration",{"count":57,"type":21},150,[59],"PHASE2","This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are \"tumor mutational burden\" and \"tumor inflammation signature.\" Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.",[62,63,34,64,65,66,67,68,69,70,71,72,35,73,74,75,76,77,78,79,80,81,82,83,84],"Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8","Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8","Locally Recurrent Head and Neck Squamous Cell Carcinoma","Locally Recurrent Hypopharyngeal Squamous Cell Carcinoma","Locally Recurrent Laryngeal Squamous Cell Carcinoma","Locally Recurrent Oral Cavity Squamous Cell Carcinoma","Locally Recurrent Oropharyngeal Squamous Cell Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hypopharyngeal Squamous Cell Carcinoma","Metastatic Laryngeal Squamous Cell Carcinoma","Metastatic Oral Cavity Squamous Cell Carcinoma","Metastatic Oropharyngeal Squamous Cell Carcinoma","Recurrent Melanoma","Stage III Hypopharyngeal Carcinoma AJCC v8","Stage III Laryngeal Cancer AJCC v8","Stage III Lip and Oral Cavity Cancer AJCC v8","Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8","Stage IV Hypopharyngeal Carcinoma AJCC v8","Stage IV Laryngeal Cancer AJCC v8","Stage IV Lip and Oral Cavity Cancer AJCC v8","Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8","Unresectable Melanoma","2026-06-25",{"date":87,"type":40},"2026-06-26",{"date":89,"type":40},"2022-12-06",{"date":91,"type":21},"2027-01-01",{"name":93,"class":94},"National Cancer Institute (NCI)","NIH",223,{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":102,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":16,"minAge":104,"maxAge":4,"enrollmentInfo":105,"targetDuration":4,"studyType":22,"phases":107,"briefSummary":108,"conditions":109,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":205,"lastUpdatePostDateStruct":206,"startDateStruct":208,"completionDateStruct":210,"leadSponsor":212,"locationsCount":48},"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":106,"type":21},132,[24,59],"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.",[110,111,112,113,114,62,115,116,117,34,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,70,148,149,150,35,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,84,195,196,197,198,199,200,201,202,203,204],"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","Anatomic Stage IV Breast Cancer 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 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 Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Merkel Cell Carcinoma","Metastatic Renal 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 III Renal Cell 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 IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer 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 Merkel Cell Carcinoma","Unresectable Renal 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":207,"type":40},"2026-06-23",{"date":209,"type":40},"2022-03-31",{"date":211,"type":21},"2028-03-31",{"name":213,"class":47},"Mayo Clinic",{"id":215,"slug":216,"hasResults":11,"nctId":217,"briefTitle":218,"officialTitle":219,"acronym":4,"eligibilityCriteria":220,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":221,"targetDuration":4,"studyType":223,"phases":4,"briefSummary":224,"conditions":225,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":228,"lastUpdatePostDateStruct":229,"startDateStruct":230,"completionDateStruct":232,"leadSponsor":234,"locationsCount":48},"100521894","evaluation-of-anti-pd-1-therapy-by-monitoring-t-cell-responses-in-melanoma-lung-and-other-cancer-types-100521894","NCT06075524","Evaluation of Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types","Maximizing Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types","Inclusion Criteria:\n\n* Are 18 years of age or older\n* Have histologic evidence of locally or regionally advanced or stage IV malignancy\n* Are considered appropriate for starting therapy with anti-PD-1\u002Fanti-PD-L1 monoclonal antibody by their treating physician (prior therapy with immune checkpoint inhibitor (ICI) is allowed)\n* Have an understanding of the protocol and its requirements, risks, and discomforts\n* Are willing to undergo peripheral blood collection at the time points mentioned in the protocol\n* Are able and willing to sign an informed consent\n\nExclusion Criteria:\n\n* Inability on the part of the patient to understand the informed consent or be compliant with the protocol\n* Patients receiving any concurrent anti-cancer therapy or investigational agents (with the exception of an anti-PD-1\u002Fanti-PD-L1 agent as mentioned above)\n* Patients who are pregnant, nursing, or are of childbearing potential and are unwilling to employ adequate contraception",{"count":222,"type":21},500,"OBSERVATIONAL","This study explores the role of T cells in monitoring disease status and response during anti-PD-1\u002FPD-L1 treatment in patients with melanoma, lung and other cancer types. Measuring levels of specific targets such as Bim and soluble PD-L1 during therapy may help track treatment resistance and clinical outcomes. This information may also help researchers determine why some people with melanoma, lung and other cancer types respond to PD-1\u002FPD-L1 treatment and others do not.",[62,34,226,132,133,227,150,35,159,176],"Locally Advanced Lung Carcinoma","Metastatic Lung Carcinoma","2026-06-16",{"date":205,"type":40},{"date":231,"type":40},"2015-06-15",{"date":233,"type":21},"2028-12-31",{"name":213,"class":47},{"id":236,"slug":237,"hasResults":11,"nctId":238,"briefTitle":239,"officialTitle":240,"acronym":4,"eligibilityCriteria":241,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":242,"targetDuration":4,"studyType":22,"phases":243,"briefSummary":244,"conditions":245,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":251,"lastUpdatePostDateStruct":252,"startDateStruct":254,"completionDateStruct":256,"leadSponsor":258,"locationsCount":259},"100508163","phase-1-immunotherapy-in-combination-with-prednisone-and-sirolimus-for-kidney-transplant-recipients-with-unresectable-or-metastatic-skin-cancer-100508163","NCT05896839","Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer","A Phase 2 Study of Nivolumab and Ipilimumab in Combination With Sirolimus and Prednisone in Kidney Transplant Recipients With Selected Unresectable or Metastatic Cutaneous Cancers","Inclusion Criteria:\n\n* Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis\n* Patient's age must be \\>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of nivolumab and ipilimumab in kidney transplant recipients \\\u003C18 years of age, children are excluded from this study, but may be eligible for future pediatric trials\n* Patients must have histologically or cytologically confirmed non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). Patients with cutaneous squamous cell carcinoma or Merkel cell carcinoma may enroll without prior medical therapy (e.g., cetuximab or chemotherapy respectively). Non-immunologic standard therapies that patients must have received, refused or for which patients were ineligible include:\n\n  * For patients with BRAF-mutant melanoma, prior therapies include BRAF\u002FMEK inhibitors\n  * For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors\n* Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \\>= 20 mm by chest x-ray or as \\>= 10 mm with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%) performance status criteria\n* Leukocytes \\>= 2,000\u002FmcL\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 50,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN\n* Serum creatinine =\\\u003C 3 x ULN\n* dd-cfDNA =\\\u003C 1.0% and =\\\u003C 61% increase\n* The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential (WOCBP) receiving nivolumab must continue contraception for a period of 5 months after the last dose of nivolumab. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.\n\nWOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of beta-human chorionic gonadotropin \\[B-HCG\\]) during the screening period. Follow-up evaluations will include interval sexual\u002Fmenstrual histories as needed.\n\nShould a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately.\n\nWOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU\u002FmL to be considered postmenopausal.\n\n* Human immunodeficiency virus (HIV)-infected patients will be eligible for this trial if they are on effective antiretroviral regimens utilizing non-CYP-interactive agents and have an undetectable viral load. If there is evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. If there is history of hepatitis C virus (HCV) infection, the patient must have been treated and have undetectable HCV viral load.\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients who have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant\n* Patients unwilling or unable to undergo dialysis in the event of allograft failure\n* Patients with prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA)\n* Patients with a history of antibody- or cell-mediated allograft rejection within 3 months of study entry\n* Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy\u002Fintervention prior to enrollment\n* Patients may have received prior anti-PD-(L)1 therapy; however, patients must not have any other checkpoint antibody targeting T-cell co-stimulation within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment. Prior receipt of oncolytic therapy (e.g., TVEC, RP1) is allowed\n* Patients must not be receiving any other investigational agents\n* Patients with leptomeningeal metastases, more than 3 untreated central nervous system (CNS) metastases, untreated brain metastases measuring \\>1cm, or requiring treatment-dose steroids (\\> 10 mg\u002Fday prednisone equivalents) for CNS-related symptoms. Exclusions are due to concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs. Patients with brain metastases meeting the above requirements are permitted to enroll\n* Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody\n* Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study\n* Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other significant condition(s) that would make this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study\n* Patients with autoimmune disease that is active or might recur and affect vital organ function will be eligible only after consultation with the study PI. Guillain-Barre (GB) syndrome, bullous skin disease, Stevens Johnson syndrome, or toxic epidermal necrolysis will be excluded\n* Patients must not have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. In addition, patients with a history of cardiac disease including coronary artery disease (CAD), myocardial infarction (MI), cardiomyopathy, arrhythmia, heart block, should have an evaluation by history pulmonary embolism (PE) and appropriate testing to allow evaluation of any events that may occur on study. These may include troponin, electrocardiogram (EKG), echocardiogram (ECHO) as clinically indicated and may include results already in the medical record if available",{"count":5,"type":21},[24,59],"This phase II trial tests the combination of nivolumab and ipilimumab with sirolimus and prednisone for the treatment of skin (cutaneous) cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started to other places in the body (metastatic) in kidney transplant recipients. Immunotherapy with nivolumab and ipilimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Sirolimus and prednisone are immunosuppressants that are given to keep the body from rejecting the transplanted kidney. Giving nivolumab and ipilimumab in combination with sirolimus and prednisone may kill more cancer cells, while also keeping the transplanted kidney healthy, in patients with unresectable or metastatic cutaneous cancer who have received a kidney transplant.",[62,246,34,247,248,249,35,151,153,250,84,195,197],"Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8","Metastatic Basal Cell Carcinoma","Metastatic Carcinoma in the Skin","Unresectable Basal Cell Carcinoma","2026-06-12",{"date":253,"type":40},"2026-06-15",{"date":255,"type":40},"2024-07-24",{"date":257,"type":21},"2027-01-31",{"name":93,"class":94},26,{"id":261,"slug":262,"hasResults":11,"nctId":263,"briefTitle":264,"officialTitle":265,"acronym":4,"eligibilityCriteria":266,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":267,"targetDuration":4,"studyType":22,"phases":269,"briefSummary":270,"conditions":271,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":274,"lastUpdatePostDateStruct":275,"startDateStruct":277,"completionDateStruct":279,"leadSponsor":281,"locationsCount":48},"100484469","phase-1-natural-killer-cell-therapy-ud-tgfbetai-nk-cells-and-temozolomide-for-the-treatment-of-stage-iv-melanoma-metastatic-to-the-brain-100484469","NCT05588453","Natural Killer Cell Therapy (UD TGFbetai NK Cells) and Temozolomide for the Treatment of Stage IV Melanoma Metastatic to the Brain","A Phase I\u002FII Study of Ex-Vivo Expanded Allogeneic Universal Donor (UD) TGFbi NK Cell Infusions in Combination With Temozolomide as a Lymphodepleting Agent in Patients With Melanoma Metastatic to the Brain","Inclusion Criteria:\n\n* Histologically confirmed melanoma with stage IV disease\n* Radiologically confirmed brain metastasis (n \\>= 1) with at least one measurable central nervous system (CNS) lesion \\>= 10 mm on T1-weighted gadolinium enhanced magnetic resonance imaging (MRI) and unequivocal evidence of progression\n* No indication for stereotactic radiotherapy\n* At least 4 weeks from any anticancer treatment (cytotoxic chemotherapy, signal transduction inhibitors, immunotherapy or radiation)\n* Absolute neutrophil count (ANC) 1 x 10\\^9\u002FL\n* Platelets \\> 100,000\u002FL\n* Hemoglobin (Hgb) \\>= 10 g\u002FdL\n* Creatinine =\\\u003C 1.5 x upper limit of normal (ULN)\n* Albumin \\>= 2.5 g\u002FdL\n* Serum bilirubin \\\u003C 1.5 x ULN unless due to Gilbert's syndrome\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 5 x ULN if documented liver metastases or \\\u003C 3 X ULN without liver metastasis\n* \\> 18 years old (y\u002Fo)\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Females of reproductive age must agree to the use of an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product for women. Males able to father a child must practice adequate methods of contraception or completely abstain from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment\n* Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and\u002For urine pregnancy test 48 hours prior to the administration of the first study treatment\n* Patient information and written informed consent form signed\n\nExclusion Criteria:\n\n* Planned or concurrent systemic treatment or radiation therapy\n* If requiring corticosteroids for cerebral edema, patients must be on a stable dose. Lowest dose of steroids needed to control CNS edema is recommended. Doses above 4 mg daily need to be cleared by principal investigator (PI) of the study\n* Known contra-indication to MRI\n* Patients with non-melanoma malignancies are excluded unless a complete remission has been achieved at least 3 years prior to study entry and no additional therapy is required or anticipated during the study period (exceptions include: non-melanoma skin cancers, in situ bladder cancer, in situ gastric cancer, in situ colon cancers, in situ cervical cancers\u002Fdysplasia, or in situ breast carcinoma)\n* Patients with other concurrent severe and\u002For uncontrolled medical disease which could compromise participation in the study, such as:\n\n  * Active infection\n  * Current active hepatic or renal disease\n  * Pregnant women, women who are likely to become pregnant or are breastfeeding\n  * Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological, or geographical conditions potentially hampering ability to consent, compliance with the study protocol, and follow-up schedule; those conditions should be discussed with the patient before remigration in the trial\n  * Patients who received any other investigational drugs within the 30 days prior to screening visit\n  * Leptomeningeal metastases diagnosed by MRI\n  * Inclusion in another therapeutic protocol within 30 days\n  * If steroids are necessary to control symptoms related to CNS metastases, patients should be on the lowest dose of steroids necessary to control symptoms",{"count":268,"type":21},24,[24,59],"This phase I\u002FII trial tests the safety, side effects, and best dose of universal donor UD TGFbetai natural killer (NK) cells, and whether UD TGFbetai NK cells with temozolomide works to shrink tumors in patients with stage IV melanoma that has spread to the brain (metastatic to the brain). NK cells are immune cells that contribute to anti-tumor immunity by recognizing and destroying transformed or stressed cells. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in the body. Giving UD TGFbetai NK cell and temozolomide may work better in treating patients with stage IV melanoma.",[34,272,35,273],"Metastatic Malignant Neoplasm in the Brain","Pathologic Stage IV Cutaneous Melanoma AJCC v8","2026-06-09",{"date":276,"type":40},"2026-06-11",{"date":278,"type":40},"2023-03-01",{"date":280,"type":21},"2027-04-15",{"name":282,"class":47},"Kari Kendra",{"id":284,"slug":285,"hasResults":11,"nctId":286,"briefTitle":287,"officialTitle":288,"acronym":4,"eligibilityCriteria":289,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":290,"targetDuration":4,"studyType":22,"phases":292,"briefSummary":293,"conditions":294,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":316,"startDateStruct":317,"completionDateStruct":319,"leadSponsor":321,"locationsCount":48},"100536473","phase-2-comparison-of-in-home-versus-in-clinic-administration-of-subcutaneous-nivolumab-through-cancer-care-connected-access-and-remote-expertise-beyond-walls-ccbw-program-100536473","NCT06265285","Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program","MC230716 Pilot Single-Arm, Pragmatic Trial Of In-Home Versus In-Clinic Subcutaneous Nivolumab Administration Through Cancer CARE (Connected Access And Remote Expertise) Beyond Walls (CCBW) Program","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Histologically confirmed malignancies for which treatment with intravenous nivolumab is currently Food and Drug Administration (FDA) approved and who are recommended to initiate a new treatment regimen with single agent intravenous (IV) nivolumab by their treating oncologist for any of the indications outlined below and who are willing to switch to subcutaneous nivolumab. Additionally, patients who are currently receiving single-agent IV nivolumab are eligible, provided they transition to subcutaneous nivolumab on-study, with their first subcutaneous (subQ) dose administered on cycle 1, day 1 of the study.\n\n  * Single agent nivolumab administered in the adjuvant setting for one of the following indications:\n\n    * Completely resected stage IIB\u002FC, III or IV melanoma\n    * Urothelial carcinoma status post radical resection and have a high risk of recurrence\n    * Completely resected esophageal or gastroesophageal junction carcinoma with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT)\n  * Single agent nivolumab for advanced\u002Fmetastatic cancer for one or more of the following indications:\n\n    * Renal cell carcinoma (RCC) patients who have received prior anti-angiogenic therapy\n    * Non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Note: patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab)\n    * Unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy\n    * Unresectable or metastatic cutaneous melanoma\n    * Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy\n    * Unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine.\n\n      * Subcutaneous nivolumab to be initiated as monotherapy following six cycles of cisplatin + gemcitabine\n    * Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Patients transitioning to maintenance nivolumab and who are willing to switch to subcutaneous nivolumab after completion of Ipilimumab and nivolumab combination therapy for one or more of the indications listed below (Note: patients who discontinue ipilimumab for immune-related toxicities, but are deemed to be eligible to continue on single agent nivolumab maintenance by their treating oncologist are eligible):\n\n    * First-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC)\n    * Unresectable or metastatic cutaneous melanoma\n    * Hepatocellular carcinoma (HCC) previously treated with sorafenib\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Single agent nivolumab administered in the adjuvant setting following neoadjuvant nivolumab with platinum doublet chemotherapy for patients with resectable (tumors ≥ 4 cm and\u002For node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements\n* Patients have recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and\u002For surgery (i.e., residual toxicity no worse than grade 1 \\[grade 2 treatment-associated peripheral neuropathy, grade 2 fatigue and\u002For any grade of alopecia are acceptable assuming all other inclusion criteria are met\\]) before registration\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* Aspartate transaminase (AST) values ≤ 3 × the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase\n* Alanine transaminase (ALT) values ≤ 3 x the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 x ULN for transaminase\n* Serum total bilirubin values of ≤ 1.5 x ULN ( ≤ 2 x ULN for patients with known Gilbert's syndrome). For patients with documented baseline liver metastasis, the following limits will apply: 2 x ULN for bilirubin\n* Absolute neutrophil count (ANC) of ≥ 1500\u002FμL\n* Platelet count of ≥ 100,000\u002FμL\n* Hemoglobin of ≥ 9 g\u002FdL (patients may be transfused to this level, if necessary, but transfusion must occur \\> 1 week prior to registration)\n* Serum creatinine ≤ 2.0 x the ULN for the reference laboratory or a calculated creatinine clearance of ≥ 30 mL\u002Fmin by the Cockcroft-Gault Equation measured ≤ 7 days prior to registration\n* Patients are residing ≤ 35 miles of clinic (hub) or within the area serviced by supplier and paramedic network\n* Residence has Wi-Fi to enable a reliable connection with the remote command center\n* Patients have signed Informed Consent Form (ICF)\n* Patients are willing and able to comply with the study protocol in the investigator's judgment\n* Patients are able and willing to complete study questionnaire(s) by themselves or with assistance\n* Women of childbearing potential (WOCBP) must:\n\n  * Have a negative pregnancy test (serum or urine) ≤ 3 days before the first dose of study drug\n  * Be agreeable to use a contraceptive method that is highly effective during the intervention period and for at least 5 months after the last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period\n\nExclusion Criteria:\n\n* Patients receiving any other investigational or standard of care agent which would be considered as a treatment for the primary neoplasm and is not part of the eligible treatment regimen\n* Patients requiring 24\u002F7 assistance with activities of daily living (ADLs)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Myocardial infarction ≤ 6 months\n  * Wound healing disorder\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Patients with any severe infection ≤ 4 weeks prior to registration including, but not limited to, hospitalization for complications of infections\n* Patients with an active, known or suspected autoimmune disease. Patients 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. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of 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 with a condition requiring systemic treatment with either corticosteroids ( \\> 10 mg daily prednisone equivalent) ≤ 14 days or other immunosuppressive medications ≤ 30 days prior to registration. Inhaled or topical steroids, and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease\n* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active ≤ 2 years prior to registration (i.e., participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization\u002Ftreatment assignment and the patient has no evidence of disease). Participants with history of prior early stage basal\u002Fsquamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible\n* Patients have undergone prior solid organ and\u002For non-autologous hematopoietic stem cell or bone marrow transplant\n* Patients with active brain metastases or leptomeningeal metastases, aside from the exceptions below. Participants with brain metastases are eligible if they are:\n\n  * Asymptomatic\n  * Have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the central nervous system \\[CNS\\] treatment), and\n  * There is no MRI evidence of progression for at least 4 weeks after CNS directed therapy is complete and ≤ 28 days prior to registration\n  * In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to registration\n* Participants with brain disease treated with whole brain radiation\n* Anticipation of the need for major surgery during the course of study treatment\n* Participants who are pregnant or breastfeeding\n* Treatment with any live attenuated vaccines ≤ 30 days of registration (vaccines that are not live attenuated are allowed, including COVID-19 vaccine)\n* Known human deficiency virus (HIV) positive with an AIDS defining opportunistic infection within the last year, or a current CD4 count \\\u003C 350 cells\u002FuL, aside from the exceptions below. Participants with HIV are eligible if:\n\n  * They have received antiviral therapy (ART) for at least 4 weeks prior to treatment assignment as clinically indicated while enrolled in the study\n  * They continue on ART as clinically indicated while enrolled on study\n  * CD4 counts and viral load are monitored per standard of care by a local healthcare provider\n* History of allergy or hypersensitivity to study drug components\n* Any positive test result for hepatitis B virus (HBV) indicating presence of virus (e.g., hepatitis B surface antigen \\[HBsAg, Australia antigen\\]) positive\n* Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV-ribonucleic acid \\[RNA\\]). Note: Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll",{"count":291,"type":21},50,[59],"This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and\u002For effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.",[295,296,297,32,33,62,298,34,299,300,301,302,143,303,304,305,306,307,70,155,308,309,310,160,311,174,177,312,313,314,199],"Advanced Esophageal Squamous Cell Carcinoma","Advanced Renal Cell Carcinoma","Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Esophageal Carcinoma","Gastroesophageal Junction Adenocarcinoma","Hepatocellular Carcinoma","Lung Non-Small Cell Carcinoma","Malignant Solid Neoplasm","Metastatic Colorectal Carcinoma","Metastatic Cutaneous Melanoma","Metastatic Esophageal Squamous Cell Carcinoma","Recurrent Esophageal Squamous Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Renal Cell Carcinoma","Stage IV Colorectal Cancer AJCC v8","Unresectable Cutaneous Melanoma","Unresectable Esophageal Squamous Cell Carcinoma","Urothelial Carcinoma","2026-06-05",{"date":274,"type":40},{"date":318,"type":40},"2024-04-30",{"date":320,"type":21},"2026-12-31",{"name":213,"class":47},{"id":323,"slug":324,"hasResults":11,"nctId":325,"briefTitle":326,"officialTitle":327,"acronym":4,"eligibilityCriteria":328,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":329,"targetDuration":4,"studyType":22,"phases":331,"briefSummary":332,"conditions":333,"keywords":4,"overallStatus":335,"whyStopped":4,"lastUpdateSubmitDate":336,"lastUpdatePostDateStruct":337,"startDateStruct":338,"completionDateStruct":340,"leadSponsor":342,"locationsCount":48},"100640848","phase-1-circadian-optimized-light-therapy-for-the-treatment-of-patients-with-advanced-melanoma-receiving-tumor-infiltrating-lymphocyte-therapy-100640848","NCT07628894","Circadian-Optimized Light Therapy for the Treatment of Patients With Advanced Melanoma Receiving Tumor-Infiltrating Lymphocyte Therapy","A Single-Center, Prospective Pilot Trial of Circadian-Optimized Light Therapy (COLT) in Patients Undergoing Tumor-Infiltrating Lymphocyte (TIL) Therapy for Metastatic Melanoma","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n* Age: ≥ 18 years\n* Ability to read and understand English for questionnaires\n* Progression on or after immune checkpoint inhibitor therapy\n* Deemed eligible and consented for standard-of-care TIL therapy (lifileucel\u002FAmtagvi)\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (typically required for TIL therapy; confirm with clinical standards of practice \\[SOP\\])\n\nExclusion Criteria:\n\n* Explicit Munich Chronotype Questionnaire (MCTQ) cutoffs (\\\u003C 2:00, \\> 5:00)\n* Use of melatonin or pharmacologic sleep aids (e.g., zolpidem, trazodone, benzodiazepines) within 14 days prior to enrollment\n* Night shift work within the past 30 days or expected during the intervention\n* Travel across ≥ 2 time zones within the past 14 days\n* Diagnosed or suspected untreated moderate to severe obstructive sleep apnea\n* History of mania, hypomania, bipolar disorder, migraine (with or without photophobia), or active seizure disorder\n* Active psychosis, suicidal ideation, or recent psychiatric hospitalization (\\\u003C 3 months)\n* Ocular conditions exacerbated by bright light exposure\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":330,"type":21},8,[24],"This phase I trial tests the effect of Circadian-Optimized Light Therapy (COLT) in conjunction with standard of care tumor-infiltrating lymphocytes (TIL) therapy in treating patients with melanoma that may have spread from where it first started to nearby tissue, lymph nodes or distant parts of the body (advanced). Circadian rhythm is the body's natural 24 hour clock which helps keep the body operating on a healthy wake-sleep cycle. Exposure to morning light has been shown to have a positive impact. Patients with advanced cancers often experience circadian disruption, including exposure to hospital-related light, treatment side effects, and inflammation. TIL are made by collecting and growing specialized T cells (a type of white blood cell) from a patient's tumor and given back to the patient to help stimulate the immune system in different ways to stop tumor cells from growing. However, disruptions in the circadian rhythm may impact the effectiveness of TIL therapy. COLT is a home-based digital intervention that delivers circadian-effective morning light using the Circadian OS iPad application. Daily light exposure may help prevent circadian disruption and improve immune and inflammatory responses. Adding COLT sessions to standard of care therapy with TIL may be safe and tolerable in patients with advanced melanoma.",[334,62,34,306],"Advanced Cutaneous Melanoma","NOT_YET_RECRUITING","2026-06-01",{"date":315,"type":40},{"date":339,"type":21},"2026-12-23",{"date":341,"type":21},"2027-07-05",{"name":343,"class":47},"City of Hope Medical Center",{"id":345,"slug":346,"hasResults":11,"nctId":347,"briefTitle":348,"officialTitle":349,"acronym":4,"eligibilityCriteria":350,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":351,"targetDuration":4,"studyType":22,"phases":353,"briefSummary":354,"conditions":355,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":384,"lastUpdatePostDateStruct":385,"startDateStruct":386,"completionDateStruct":388,"leadSponsor":390,"locationsCount":48},"100442316","phase-1-iacs-6274-with-or-without-bevacizumab-and-paclitaxel-for-the-treatment-of-advanced-solid-tumors-100442316","NCT05039801","IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors","A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors","Inclusion Criteria All Parts\n\n1. Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n2. Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.\n3. Histologically or cytologically confirmed advanced solid tumors, specifically:\n\n   Dose Escalation for Part A may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2\u002FSTK11\u002FNF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \\[or equivalent of 2 response evaluations\\]).\n\n   Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer\n\n   Dose Escalation for Part B may include:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \\\u003C 6 months, and with less than 5 prior therapies\n\n   Dose Expansion for Part B limited to:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \\\u003C 6 months, and with less than 5 prior therapies.\n\n   Dose Escalation for Part C may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1\u002FNFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)\n\n   Dose Expansion for Part C limited to:\n\n   Patients with NSCLC with actionable KEAP1\u002FNFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1\u002FNFE2L2)\n4. Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.\n5. Prior treatment with chemotherapy, radiotherapy, immunotherapy or any investigational therapies must have been completed at least 3 weeks or at least five half lives, whichever is shorter, before the study drug administration, and all AEs (excluding alopecia and peripheral neuropathy) have either returned to ≤Grade 1 or stabilized. Patients with concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) are allowed.\n6. Fresh and\u002For archival tumor tissue from a biopsy obtained between the completion of the most recent line of treatment until study entry must be available for mutation and biomarker analysis. If available, archival tumor tissue from the time of initial diagnosis or the most recent biopsy (archival and\u002For fresh) will be collected. For ovarian cancer patients, a fresh biopsy must be collected in addition to archival tumor tissue. NOTE: No fresh tumor tissue will be required if a previous biopsy detected the selected mutations for each cohort. In all cases, procedures to obtain fresh tumor tissue should not put the patient at undue risk, and should only be performed if the risk is minimal (no greater than 2% risk of serious or severe complications).\n7. Patients must have at least 1 lesion (measurable and\u002For non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessments.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n9. Adequate organ function as indicated by the following laboratory values:\n\n   Absolute neutrophil count (ANC) ≥1.0×109\u002FL Platelets ≥100×109\u002FL Hemoglobin ≥9.0 g\u002FdL (\\>5.59 mmol\u002FL) Creatinine clearance (CrCl) \\>50 mL\u002Fmin. Actual body weight should be used for calculating creatinine clearance using the Cockroft Gault equation (except for patients with body mass index \\>30 kg\u002Fm2 when the lean body weight should be used, and without the need for chronic dialysis therapy).\n\n   Serum total bilirubin ≤1.5×ULN (with the exception of patients with known thalassemia minor mutations or Gilbert's syndrome: serum total bilirubin must be \\\u003C3×ULN in these patients) Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN for patients with liver metastases)\n10. Adequate cardiac function with a left ventricular ejection fraction ≥50%\n11. Female patients of non childbearing potential, who are physiologically incapable of becoming pregnant, are eligible to enter and participate in the study if they:\n\n    have had a hysterectomy, OR have had a bilateral oophorectomy, OR have had a bilateral salpingectomy, OR is postmenopausal (total cessation of menses for ≥2 years, or follicle stimulating hormone ≥50 IU\u002FL).\n12. Female patients of childbearing potential, who are not post-menopausal or surgically sterile and intent to be sexually active with a non-sterile male partner, are required to use one form of highly effective contraception combined with a barrier method (male condom, female condom, cervical cap, diaphragm with spermicide, or contraceptive sponge with spermicide) of contraception starting before entering the study and until 4 weeks after the last dose of treatment.\n\n    Highly effective non-hormonal contraceptive methods that are acceptable include:\n\n    Total\u002Ftrue abstinence\\*\\*\\* for the total duration of the study treatment and for at least 1 month after the last dose of study treatment. Periodic abstinence using methods such as calendar ovulation, symptothermal, post ovulation methods, declaration of abstinence solely for the duration of a trial, or withdrawal are not acceptable methods of contraception.\n\n    Having a vasectomized sexual partner, who received post-vasectomy confirmation of azoospermia, combined with a barrier method as described above.\n\n    Bilateral tubal occlusion combined with a barrier method as described above. Intrauterine device with copper banded coils, combined with a barrier method as described above.\n\n    Highly effective hormonal contraceptive methods that are acceptable include:\n\n    Combined oral pill contraception (normal and low-dose oral pills, or progesterone-based oral pills using desogestrel) combined with a barrier method as described above. NOTE: cerazette is currently the only highly efficacious progesterone-based pill available.\n\n    Injection (e.g., medroxyprogesterone) combined with a barrier method as described above.\n\n    Patch (e.g., norelgestromin or ethinyl estradiol transdermal system) combined with a barrier method as described above.\n\n    Implants (etonorgestrel-releasing) combined with a barrier method as described above.\n\n    Intravaginal device (e.g., ethinyl estradiol- or etonogestrel-releasing) combined with a barrier method as described above.\n\n    Intrauterine system (levonorgestrel-releasing) combined with a barrier method as described above.\n\n    In addition to the to use one form of highly effective contraception combined with a barrier method, female patients of childbearing potential must have a negative serum pregnancy test at screening (within 7 days of the start of treatment) and must not be breastfeeding.\n13. Non-sterile men, who are not sexually abstinent and intend to be sexually active with a woman of childbearing potential, must use a condom from the start of the trial and until 16 weeks after the last dose of treatment, or must practice total abstinence\\*\\*\\* for the total duration of the study treatment and at least 3 months after the last dose of study treatment. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of childbearing potential should consider the use of at least one contraception method describe above. If the female partner is pregnant, male participants should use a condom plus spermicide.\n\n    * Total\u002Ftrue abstinence is defined as a patient who refrains from any form of sexual intercourse, and this is in line with their usual and\u002For preferred lifestyle.\n\nExclusion Criteria All Parts\n\n1. Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.\n2. Known primary central malignancy or symptomatic central nervous system metastasis(es).\n\n   Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.\n3. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:\n\n   1. Any unstable cardiac arrhythmia within 6 months prior to enrolment\n   2. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \\>450 ms for males and \\>470 ms for females\n   3. History of any of the following cardiovascular conditions within 6 months of enrolment:\n\n      * cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.\n4. Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.\n5. Significant acute or chronic infections.\n6. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.\n7. Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.\n8. Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.\n9. Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.\n10. Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.\n11. History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the compounds in the study.\n12. Known history of alcohol or drug abuse.\n13. Legal incapacity or limited legal capacity.\n14. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses (such as refractory nausea and vomiting, chronic gastrointestinal disease or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretionof IACS-6274 and capivasertib, which are oral agents.\n15. Patients unwilling to comply with protocol requirements related to the assigned part.\n16. Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.\n\nPart B Specific Exclusion Criteria (B1) Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, three or more features of partially controlled asthma).\n\n(B2) Patient has a known hypersensitivity to paclitaxel or bevacizumab components or excipients.\n\n(B3) Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n(B4) Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate \\\u003C2 g of protein in 24 hours to be eligible).\n\n(B5) Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).\n\n(B6) Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. (B7) Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.\n\n(B8) Patient requires paracentesis 2 weeks prior to trial enrolment. Part C Specific Exclusion Criteria (C1) History of another primary malignancy, except for a malignancy treated with curative intent, with no known active disease ≥5 years before the first dose of treatment, with low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.\n\n(C2) Patient has a known hypersensitivity to capivasertib components or any excipients of the product.\n\n(C3) Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management), Glycosylated haemoglobin (HbA1c) \\>8% (64 mmol\u002Fmol) (C4) Patients with evidence of severe or uncontrolled systemic liver disease including severe hepatic impairment, or abnormal liver enzymes at screening (AST or ALT \\>2.5 x ULN; total bilirubin \\>1.5 x ULN).\n\n(C5) Patients with elevated alkaline phosphatase (ALP) can be enrolled if the abnormal value is due to the presence of bone metastasis, but liver function is considered adequate according to the principal investigator.\n\n(C6) Patients with persistent toxicities (Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included after consultation with the sponsor and the study physician.\n\n(C7) Patients with spinal cord compression or leptomeningeal disease not requiring steroids for at least 4 weeks prior to start of study intervention.\n\n(C8) Patients with clinically significant cardiovascular disease including, but not limited to, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. In addition, patients will be excluded based on the study physician's judgment of the following criteria:\n\n* Mean resting corrected QT interval \\>470ms, obtained from triplicate ECGs performed at screening.\n* Medical history significant for arrhythmia that is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation regardless of treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be included based on the study physician's judgment.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia of Grade ≥1, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relative, history of QT prolongation associated with other medications that required discontinuation of the medication.\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ≥2.\n* Uncontrolled hypotension: SBP \\\u003C90 mmHg and\u002For DBP \\\u003C50 mmHg.\n* Cardiac ejection fraction outside institutional range of normal or \\\u003C50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \\[MUGA\\] scan if an echocardiogram cannot be performed or is inconclusive).\n\n(C9) Patients with active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) are excluded.\n\n(C10) Patients with active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening are excluded.\n\nHuman immunodeficiency virus (HIV) positive patients with a viral load \\> 400 copies\u002FmL and a CD4+ T-cell count of \\\u003C350 cells\u002FuL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months are excluded. Patients with a higher viral load or lower CD4+ count (\\\u003C 350 cells\u002FuL) may be considered for eligibility if the patient has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.\n\nHIV-positive patients receiving antiretroviral therapies should be on established ART for at least four weeks before starting treatment to ensure that treatment is tolerated and that toxicities are not confused with investigational drug toxicities. HIV-positive patients receiving antiretroviral therapies that are strong CYP3A4\u002F5 inhibitors\u002F inducers or sensitive substrates of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib.\n\n(C12) Patients who are undergoing any concurrent anticancer treatment or any concomitant medication that may interfere with the study drugs according to local clinical guidelines are excluded.\n\n(C13) Patients who received palliative radiotherapy within 2 weeks prior to the start of study treatment; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the start of study treatment are excluded.",{"count":352,"type":21},54,[24],"To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.",[356,357,358,359,360,361,62,34,362,363,364,365,366,273,367,368,369,370,371,372,373,374,375,164,376,377,378,168,379,170,171,172,380,381,382,181,383,185],"Advanced Endometrial Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Ovarian Clear Cell Adenocarcinoma","Chondrosarcoma","Pathologic Stage III Cutaneous Melanoma AJCC v8","Pathologic Stage IIIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Recurrent Ovarian High Grade Serous Adenocarcinoma","Refractory Endometrial Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Melanoma","Refractory Ovarian Clear Cell Adenocarcinoma","Refractory Ovarian High Grade Serous Adenocarcinoma","Stage III Ovarian Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","2026-05-29",{"date":336,"type":40},{"date":387,"type":40},"2021-09-30",{"date":389,"type":21},"2028-06-30",{"name":391,"class":47},"M.D. Anderson Cancer Center",{"id":393,"slug":394,"hasResults":11,"nctId":395,"briefTitle":396,"officialTitle":397,"acronym":4,"eligibilityCriteria":398,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":399,"targetDuration":4,"studyType":22,"phases":400,"briefSummary":401,"conditions":402,"keywords":4,"overallStatus":335,"whyStopped":4,"lastUpdateSubmitDate":414,"lastUpdatePostDateStruct":415,"startDateStruct":417,"completionDateStruct":419,"leadSponsor":421,"locationsCount":48},"100638080","phase-2-low-dose-reduced-frequency-nivolumab-for-the-treatment-of-unresectable-or-metastatic-cancer-afford-io-trial-100638080","NCT07576725","Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial","AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer","Inclusion Criteria:\n\n* Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents\n\n  * Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \\[CPS\\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations\u002Frearrangements, including EGFR, ALK and ROS-1, will be excluded.)\n  * Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)\n  * Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)\n  * Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \\[CSCC\\], basal cell carcinoma \\[BCC\\] and Merkel cell carcinoma \\[MCC\\])\n  * Hodgkin's lymphoma\n  * Urothelial carcinoma\n  * Cervical cancer with documented PD-L1 expression (CPS ≥ 1)\n  * Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency\n  * Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)\n  * Any cancer type with historical data suggesting an ORR \\> 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)\n* Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options\n* Presence of at least one measurable tumor, per RECIST v1.1\n* Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)\n* Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n* Absolute neutrophil count (ANC) ≥ 1.0 × 10\\^9\u002FL\n* Platelet count ≥ 75 × 10\\^9\u002FL\n* Hemoglobin ≥ 9 g\u002FdL (NOTE: Participants may have been transfused)\n* Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \\[ULN\\] in participants with Gilbert's syndrome)\n* Estimated creatinine clearance ≥ 30mL\u002Fmin according to the Cockcroft-Gault formula or according to local institutional standard\n* Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator\n* Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)\n* Women of childbearing potential must have a negative serum or urine pregnancy test at screening\n* Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists\n\nExclusion Criteria:\n\n* Prior exposure to any immune-checkpoint inhibitor for any reason\n* Residual adverse event(s) from prior therapy grade \\> 1 (National Cancer Institute \\[NCI\\]-Common Terminology Criteria for Adverse Events \\[CTCAE\\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator\n* Known active central nervous system (CNS) metastases and\u002For prior history of leptomeningeal cancer involvement\n* Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \\[skin, bladder, cervical, colorectal, breast\\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:\n\n  * Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \\[DNA\\] is negative, this participant could be enrolled with close monitoring of HBV activities.)\n  * Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)\n* Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100\u002FμL, viral load less than 200 copies\u002FmL, and clinically stable on antiretroviral therapy \\[ART\\] for at least 3 months.)\n\n  * These participants will be enrolled only after approval from the medical monitor\n* Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses \\\u003C 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \\[e.g., contrast dye allergy\\], nivolumab-related standard premedication, and\u002For treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk\u002Fbenefit assessment.)\n* Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities\n* Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk\u002Fbenefit assessment.)\n* Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis\n* Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study\n* Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \\[chickenpox\\], yellow fever, rabies, bacillus Calmette Guerin \\[BCG\\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)\n* Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study\n* Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)\n* Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk\n* Pregnant or breast-feeding woman",{"count":291,"type":21},[59],"This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.",[62,246,34,247,403,404,405,248,144,406,305,306,70,407,149,150,151,408,153,155,157,409,203,159,160,173,311,204,176,177,410,250,187,411,412,312,191,193,194,195,413,197,199],"Hodgkin Lymphoma","Kaposi Sarcoma","Metastatic Acral Lentiginous Melanoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Kaposi Sarcoma","Metastatic Mucosal Melanoma","Stage III Colorectal Cancer AJCC v8","Unresectable Acral Lentiginous Melanoma","Unresectable Clear Cell Renal Cell Carcinoma","Unresectable Colorectal Carcinoma","Unresectable Mucosal Melanoma","2026-05-01",{"date":416,"type":40},"2026-05-08",{"date":418,"type":21},"2026-09-01",{"date":420,"type":21},"2029-08-31",{"name":422,"class":47},"Fred Hutchinson Cancer Center",{"id":424,"slug":425,"hasResults":11,"nctId":426,"briefTitle":427,"officialTitle":428,"acronym":4,"eligibilityCriteria":429,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":430,"targetDuration":4,"studyType":22,"phases":432,"briefSummary":433,"conditions":434,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":435,"lastUpdatePostDateStruct":436,"startDateStruct":438,"completionDateStruct":440,"leadSponsor":442,"locationsCount":48},"100441332","phase-2-binimetinib-and-encorafenib-for-the-treatment-of-metastatic-melanoma-and-central-nervous-system-metastases-100441332","NCT05026983","Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases","Phase II Study of Binimetinib With Encorafenib in Patients With Metastatic Melanoma and CNS Metastases","Inclusion Criteria:\n\n* Able to provide written informed consent.\n* Age \\>= 18 years at the time of informed consent\n* Histologically confirmed diagnosis of melanoma\n* Presence of BRAFV600 mutation in tumor tissue previously determined by a local assay (including immunohistochemistry \\[IHC\\]) at any time prior to Screening or during Screening\n* Cohort A: BRAF V600 mutant melanoma patients with progressive central nervous system (CNS) metastases. This includes patients with parenchymal brain metastases and\u002For LMD\n* Cohort A: Prior therapy with Food and Drug Administration (FDA)-approved BRAF inhibitors (+\u002F- MEK inhibitors) is required\n\n  * No washout period is required\n* Cohort A: Prior therapy with immunotherapy or other investigational agents is allowed\n\n  * Washout period of 14 days since last dose\n* Cohort B: BRAF V600 mutant melanoma patients who are treatment naive to BRAF\u002FMEK inhibitors with CNS metastases, including LMD. Prior treatment with immunotherapy is permitted\n* For patients with parenchymal brain metastases (mets) without LMD\n\n  * Metastatic disease to the brain with at least 1 progressing parenchymal brain lesion \\>= 0.5 cm and =\\\u003C 3 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately measured in at least 1 dimension\n* For patients with LMD\n\n  * Patients must have investigator assessed radiographic and\u002For CSF cytological evidence of LMD\n* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =\\\u003C 2\n* Patients may receive steroids to control symptoms related to CNS involvement\n\n  * For patients with parenchymal brain metastases the dose must be =\\\u003C 2 mg per 24 hours of dexamethasone (or the equivalent). Patient's symptoms should experience stability of neurological symptoms for at least 7 days, or on tapering dose of steroids. Physiologic replacement doses for adrenal insufficiency is allowed on this protocol\n  * For patients with LMD: the dose must be =\\\u003C 4 mg per 24 hours of dexamethasone (or the equivalent). Physiologic replacement doses for adrenal insufficiency is allowed on this protocol\n* Radiation therapy:\n\n  * For patients with parenchymal brain mets: prior radiation therapy, including stereotactic (SRS) or whole brain radiation (WBXRT) is allowed, but patient must be progressing in or having at least 1 new CNS lesion. Prior SBRT to extracranial lesions is allowed. Washout to prior radiation 14 days.\n  * For patients with LMD: Patients who have received radiation to brain and\u002For spine, including WBXRT, SRS, or SBRT, are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment.\n* Prior therapy with systemic immunotherapy or other investigational agents is allowed\n\n  * Washout period of 14 days since last dose\n* Other cancer directed treatment:\n\n  * Concurrent treatment with other anti-cancer systemic therapies is not allowed. No other concomitant intrathecal therapy with another agent will be allowed. For patients that have received other systemic therapies, the minimum wash out period is as follows:\n\n    * Patients that received previous intrathecal therapy must have received their last treatment \\>= 7 days prior to the start of treatment\n    * Patients who have received systemic chemotherapy must have received their last treatment \\>= 21 days prior to the start of treatment\n\nPatients must have appropriate laboratory parameters as defined below:\n\n* Absolute neutrophil count (ANC) 1.5 X 10\\^9\u002FL\n* Hemoglobin 9.0 g\u002FdL\n* Platelets 75 X 10\\^9\u002FL\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) and partial thromboplastin time (PTT) =\\\u003C 1.5 X upper limit of normal (ULN)\n* Total bilirubin =\\\u003C 1.5 X ULN (isolated bilirubin \\> 1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin \\\u003C 35%)\n\n  * NOTE: Patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the primary investigator\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X ULN, in patients with liver metastases ≤5 X ULN\n* Albumin ≥2.5 g\u002FdL\n* Creatinine ≤ 1.5 X ULN OR calculated creatinine clearance ≥50 mL\u002Fmin OR 24-hour urine creatinine clearance ≥50 mL\u002Fmin\n* Female patients of childbearing potential must have a negative serum and\u002For urine pregnancy test result\n* Female patients of childbearing potential must agree to protocol-approved methods of contraception and to not donate ova from Screening until 30 days after the last dose of study drug. Male patients must agree to use methods of contraception that are highly effective or acceptable and to not donate sperm from Screening until 90 days after the last dose of study drug\n* The patient is deemed by the Investigator to have the initiative and means to comply with scheduled visits, treatment plan and study procedures\n\nExclusion Criteria:\n\n* Evidence of active infection =\\\u003C 7 days prior to initiation of study drug therapy (does not apply to viral infections that are presumed to be associated with the underlying tumor type required for study entry)\n* Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 30 days of prior to study drug. Dead virus vaccines (e.g Flu) are allowed, even during treatment with study drug\n* Inability to swallow and retain study treatment\n* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on antiretroviral therapy (ART)\n* Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, the following:\n\n  * History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \\\u003C 6 months prior to screening\n  * Congestive heart failure requiring treatment (New York Heart Association grade \\>= 2)\n  * A left ventricular ejection fraction (LVEF) \\\u003C 50% as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)\n  * History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)\n  * Baseline Fridericia's correction formula (QTcF) interval \\>= 480 msec. Can be repeated up to three times to confirm\n* Concurrent neuromuscular disorder (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)\n* Impairment of gastrointestinal function or disease which may significantly alter the absorption of study treatment (e.g., uncontrolled nausea, vomiting or diarrhea; malabsorption syndrome; small bowel resection). Known history of acute or chronic pancreatitis\n* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease\n* Use of herbal supplements, medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A4\u002F5 =\\\u003C 1 week prior to the start of study treatment\n* History of a thromboembolic event \\\u003C 12 weeks prior to starting study treatment. Examples of thromboembolic events include transient ischemia attack, cerebrovascular accident, deep vein thrombosis or pulmonary embolism. Catheter-related venous thrombosis is not considered a thromboembolic event for this trial even if \\\u003C 12 weeks prior to starting study treatment. Note: Patients with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are stable, asymptomatic and on stable anticoagulants for at least 2 weeks. Additionally, patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled\n* Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection\n\n  * NOTE: Patients with laboratory evidence of cleared HBV or HCV infection may be enrolled\n  * NOTE: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may enroll\n* Pregnancy or breastfeeding or patients who plan to become pregnant during the duration of the study\n* Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study",{"count":431,"type":21},35,[59],"This phase II trial studies the effects of binimetinib and encorafenib in treating patients with melanoma that has spread to the central nervous system (metastases). Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may help control melanoma that has spread to the brain.",[34,35,273],"2026-04-13",{"date":437,"type":40},"2026-04-16",{"date":439,"type":40},"2021-12-27",{"date":441,"type":21},"2027-02-02",{"name":391,"class":47},{"id":444,"slug":445,"hasResults":11,"nctId":446,"briefTitle":447,"officialTitle":448,"acronym":4,"eligibilityCriteria":449,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":450,"targetDuration":4,"studyType":22,"phases":452,"briefSummary":453,"conditions":454,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":467,"lastUpdatePostDateStruct":468,"startDateStruct":470,"completionDateStruct":472,"leadSponsor":474,"locationsCount":48},"100446805","phase-1-personalized-neo-antigen-peptide-vaccine-for-the-treatment-of-stage-iiic-iv-melanoma-hormone-receptor-positive-her2-negative-metastatic-refractory-breast-cancer-or-stage-iii-iv-non-small-cell-lung-cancer-100446805","NCT05098210","Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer","PNV21-001: A Phase I Study of a Personalized Multi-Peptide Neo-Antigen Vaccine in Breast Cancer, PD1\u002FPD-L1 Inhibitor-Refractory Melanoma, and Pretreated Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Female and\u002For male patients age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2\n* Patients must have at least 1 lesion (or aggregate lesions) to obtain tumor tissue for resection of \\>= 1 cm or \\>= 4 core biopsies acceptable. Amenable to image (CT, ultrasound \\[U\u002FS\\], or magnetic resonance imaging \\[MRI\\]) guided biopsy for tissue collection necessary for neoantigen identification. Either primary or metastatic sites are options for tissue collection\n* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \\>= 10 mm, unless lymph node in which case short axis must be \\>= 15 mm. Baseline imaging (for example diagnostic CT chest\u002Fabdomen\u002Fpelvis, PET CT scan and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 45 days of prior to start of first planned vaccine dose infusion. MRI can be substituted for CT in patients unable to have CT contrast\n* Serum creatine \\\u003C 1.5 mg\u002FdL or estimated glomerular filtration rate (eGFR) \\> 60 mL\u002Fmin\n* Total bilirubin (tBili) \\\u003C 1.5 x upper limit of normal (ULN) and an aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) \\\u003C 2.5 x ULN and \\\u003C 5 x ULN for subjects with documented liver metastasis. Patients with suspected Gilbert syndrome may be included if tBili \\> 3 but no other evidence of hepatic dysfunction\n* =\\\u003C grade 1 dyspnea and arterial oxygen saturation (SaO2) \\>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \\>= 70% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \\>= 60% of predicted will be eligible\n* Patients with active interstitial lung disease (ILD)\u002Fpneumonitis or a history of ILD\u002Fpneumonitis requiring treatment with systemic steroids will be excluded\n* Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \\>= 50%. Cardiac evaluation for other patients is at the discretion of the treating physician\n* 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 will be excluded\n* Absolute neutrophil count (ANC) \\> 1000 cells\u002Fmm\\^3\n* Hemoglobin \\>= 9 mg\u002FdL\n* Platelet count \\>= 50,000\u002FuL\n* Toxicity from prior therapy must be recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5 grade 2 or less\n* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures\n* Capable of understanding and providing a written informed consent\n* The effects of neoantigen vaccination on the developing human fetus are unknown. For this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation. Should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment\n* MELANOMA SPECIFIC: Tissue confirmation of melanoma: Histologically confirmed metastatic (recurrent or de novo stage IV) or unresectable locally advanced (stage IIIC or IIID) cutaneous, acral, conjunctival or mucosal melanoma, as defined by the American Joint Committee on Cancer (AJCC) v8.0. Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Center (FHCC)\u002FUniversity of Washington Medical Center (UWMC)\n* MELANOMA SPECIFIC: Patients must have received stage specific standard of care therapy per National Comprehensive Cancer Network (NCCN) guidelines and have persistent\u002Frecurrent disease after at least one line of therapy prior to enrollment on the study\n* MELANOMA SPECIFIC: Known BRAF mutational status\n* MELANOMA SPECIFIC: History of detectable disease during\u002Fafter treatment with a PD-1 or PD-L1 inhibitor, as defined by the Society of Immunotherapy of Cancer's definition of primary or secondary resistance (Kluger and others \\[et al.\\], 2020):\n\n  * Drug exposure \\>= 6 weeks and best response progressive disease (PD) or stable disease (SD) \\\u003C 6 months or\n  * Drug exposure \\>= 6 months and best response complete response (CR), partial response (PR), or SD \\> 6 months\n* MELANOMA SPECIFIC: A confirmatory scan performed at least 4 weeks after disease persistence\u002Fprogression is required but this requirement can be waived if the judgement of the treating clinician is that the patient would be at risk of rapid or symptomatic progression in that interval. This confirmatory scan can occur during production of the vaccine after enrollment\n* BREAST CANCER SPECIFIC: Tissue confirmation of stage IV (recurrent or de novo metastatic) hormone receptor (HR) positive, HER2 negative breast cancer:\n\n  * Hormone receptor (HR) positive breast cancer as defined by either one, or both of the following criteria:\n\n    * Estrogen receptor (ER) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n    * Progesterone receptor (PR) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n  * Human epidermal growth factor receptor 2 (HER2) negative breast cancer (per American Society of Clinical Oncology \\[ASCO\\]\u002FCollege of American Pathologists \\[CAP\\] guideline update, 2018) as documented by a local laboratory with HER2-negativity defined as:\n\n    * Immunohistochemistry score 0\u002F1+ or 2+ and \u002F or\n    * Negative by in situ hybridization (fluorescence in situ hybridization \\[FISH\\]\u002Fchromogenic in situ hybridization \\[CISH\\]\u002Fsilver-enhanced in situ hybridization \\[SISH\\]) per ASCO\u002FCAP guideline update, 2018\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* BREAST CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic setting prior to enrollment on the study and have progressive\u002Fpersistent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Tissue confirmation of stage III unresectable or stage IV (recurrent or de novo metastatic) non-small cell lung cancer (NSCLC):\n\n  * Genetic testing must have been performed for targetable driver mutations, including EGFR, ROS1, Alk, KRAS, BRAF\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic or stage II or III setting including a PD-1 or PD-L1 inhibitor prior to enrollment on the study and have progressive or recurrent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: For patients who have received neoadjuvant, adjuvant, and\u002For consolidation anti-PD-1 or anti-PD-L1 for stage II or III disease, they must have experienced disease progression in less than or equal to 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy for this to count as the systemic therapy for advanced disease. Patients experiencing progression more than 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy will not be considered as having received one line of systemic therapy. These patients must have received an anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease\n\nExclusion Criteria:\n\n* Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 5 months after the last dose of investigational product\n* Any history of an immune-related grade 4 adverse event attributed to prior cancer immunotherapy CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)\n* Any history of an immune-related grade 3 adverse event attributed to prior CIT that required permanent discontinuation of PD-1 inhibitor therapy\n* Immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not resolved to baseline. Patients treated with corticosteroids for immune-related adverse events must demonstrate absence of related symptoms or signs for \\>= 4 weeks following discontinuation of corticosteroids\n* Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated \\> 4 weeks prior to enrollment. Patients should be recovered from the effects of radiation\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed\n* Patients with known symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable for \\>= 1 months (confirmed by magnetic resonance imaging \\[MRI\\])\n* Patients with rapidly progressing disease, symptomatic visceral disease, or patients who are expected to have rapidly progressive disease over the course of several months despite bridging therapy approved by the protocol\n* Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \\[SCID\\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)\n* Prior allogeneic bone marrow transplantation or prior solid organ transplantation\n* Known positive test for HIV infection\n* Patients with active infection causing fever (temperature \\> 38.1 degrees Celsius \\[C\\]) or subjects with unexplained fever (temperature \\> 38.1 degrees C) may not receive the investigational product unless the fever is =\\\u003C 38.1 for 5 days prior to start\n* Active uncontrolled infection: individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication (e.g., AST and ALT \\\u003C 5 x ULN) can be included\n* History of autoimmune disease that has not been controlled with treatment in the last 12 months, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions: Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible\n* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \\> 10 mg\u002Fday or equivalent, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-alpha antagonists) within 2 weeks prior screening. The use of topical, eye drops, local injections, or inhaled corticosteroids (e.g. fluticasone for chronic obstructive pulmonary disease) is allowed. The use of oral mineralocorticoids (e.g. fludrocortisone for patients with orthostatic hypotension) is allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed. Low dose corticosteroids for a short duration \\[5 mg once daily (QD) prednisone for 2 weeks\\] as symptomatic treatment and upon with discussion with the investigator is allowed. Note: Patients with adrenal insufficiency may take 10 mg of prednisone or equivalent daily\n* Subjects should have an international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\\\u003C 1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy should have a prothrombin time (PT) or partial thromboplastin time (PTT) within therapeutic range of intended use and no history of severe hemorrhage. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered anticoagulants for the purposes of this study (i.e., they are allowed)\n* Other medical, social, or psychiatric factor that interferes with medical appropriateness and\u002For ability to comply with study, as determined by the principal investigator (PI)\n* Participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)\n* Female patients who are lactating or intend to breastfeed during the duration of the study\n* Patients who have received a live vaccine within 30 days prior to enrollment\n* Patients with any underlying medical condition for which, in the investigator's opinion, participation would not be in the best interest of the participant (e.g.- compromises the health of the subject) or that could prevent, limit or confound protocol assessments\n* MELANOMA SPECIFIC: Uveal or choroidal melanoma. This entity is excluded due to the absence of abundant mutations\n* BREAST SPECIFIC: Patients with symptomatic disease including patients with symptomatic lung metastases, bone marrow replacement with associated cytopenia, or significant liver metastases with associated liver dysfunction\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Activating mutations in EGFR or genetic alterations in ROS1 or Alk, as these mutations are associated with lower mutation burden and non-response to immune therapies",{"count":451,"type":21},25,[24],"This phase I trial studies the safety of personalized neo-antigen peptide vaccine in treating patients with stage IIIC-IV melanoma, hormone receptor positive HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or does not respond to treatment (refractory) or stage III-IV non-small cell lung cancer. Personalized neo-antigen peptide vaccine is a product that combines multiple patient specific neo-antigens. Given personalized neo-antigen peptide vaccine together with Th1 polarizing adjuvant poly ICLC may induce a polyclonal, poly-epitope, cytolytic T cell immunity against the patient's tumor.",[114,34,455,456,457,458,306,459,460,149,150,408,365,366,461,462,463,464,465,159,176,466,312,193,413],"Locally Advanced Cutaneous Melanoma","Locally Advanced Mucosal Melanoma","Metastatic Acral Melanoma","Metastatic Conjunctival Melanoma","Metastatic HER2-Negative Breast Carcinoma","Metastatic Hormone Receptor-Positive Breast Carcinoma","Recurrent Cutaneous Melanoma","Recurrent HER2-Negative Breast Carcinoma","Recurrent Hormone Receptor-Positive Breast Carcinoma","Recurrent Lung Non-Small Cell Carcinoma","Recurrent Mucosal Melanoma","Unresectable Acral Melanoma","2026-03-10",{"date":469,"type":40},"2026-03-12",{"date":471,"type":40},"2022-06-09",{"date":473,"type":21},"2028-11-01",{"name":422,"class":47},{"id":476,"slug":477,"hasResults":11,"nctId":478,"briefTitle":479,"officialTitle":480,"acronym":4,"eligibilityCriteria":481,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":482,"targetDuration":4,"studyType":22,"phases":484,"briefSummary":485,"conditions":486,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":467,"lastUpdatePostDateStruct":507,"startDateStruct":509,"completionDateStruct":511,"leadSponsor":513,"locationsCount":48},"100348630","phase-1-role-of-gut-microbiome-and-fecal-transplant-on-medication-induced-gi-complications-in-patients-with-cancer-100348630","NCT03819296","Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Cancer","Role of Microbiome in the Realm of Immune-Checkpoint Inhibitor Induced GI Complications In Cancer Population","Inclusion Criteria:\n\n1. Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU) malignancies (Project 1).\n2. Diagnosis of any cancer type (Projects 2 and 3)\n3. Treatment with any ICPI agent\n4. Ability to understand and willingness to sign an informed consent form and rate surveys\n5. Life expectancy \\> 4 months (Project 3)\n6. ICPI-related diarrhea and\u002For colitis of any grade with or without concurrent non- GI toxicity as the toxicity group (project 1)\n7. Patients with no organ toxicity as the control group (project 1)\n8. ICPI-related colitis and\u002For diarrhea of grade ≥ 2 as GI toxicity (initial episode or recurrence) receiving standard treatment of immunosuppressive agents (steroid, infliximab, vedolizumab, or ustekinumab) any time during the colitis disease course until sustained resolution of GI toxicity, or one- year time point after enrollment (Project 2)\n9. ICPI-related colitis and\u002For diarrhea of grade ≥ 2 as GI toxicity without involvement of non- GI toxicity within 45 days prior to FMT (Project 3)\n10. ICPI-related colitis and\u002For diarrhea of grade ≥ 2 within 45 days prior to FMT with ANY of the following characteristics (project 3):\n\n    (i) refractory to treatment of steroid and two doses of non-steroidal immunosuppressants e.g. infliximab, vedolizumab or ustekinumab,\n\n    (ii) contraindication for immunosuppressive treatment,\n\n    (iii) recurrence after successful initial treatment,\n\n    (iv) recurrent symptoms once steroid is tapered down\u002Foff or diarrhea\u002Fcolitis symptoms are steroid dependent, or\n\n    (v) patients with a history of refractory ICPI-related colitis and\u002For diarrhea to medical treatment, even if they have improved symptoms from supportive care within 45 days prior to FMT\n11. No concern for active concomitant GI infection for the ICPI diarrhea\u002Fcolitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation (project 3)\n12. Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea\u002Fcolitis treatment (project 3)\n\nExclusion Criteria:\n\n1. Age younger than 18 years\n2. History of inflammatory bowel disease, and\u002For radiation enteritis or colitis with active disease status at the time of study treatment initiation\n3. Pregnant and breastfeeding women\n4. Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was \\> 1 year prior to consent and\u002F or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to date of study treatment\n5. Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project 3)\n6. Patients with active bacterial or fungal infection (Project 3)\n7. Donors at risk for monkeypox infection and\u002F or exposure as determined by a questionnaire (Project 3)\n\nWithdrawal Criteria\n\n1. Patients may withdraw from the trial at any time\n2. Patients who develop GI perforation or toxic colitis that require surgery from ICPI colitis\n3. In project 3, if the first 30% of cases fail the fecal transplant treatment, then project 3 will be terminated",{"count":483,"type":21},800,[24],"This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on medication-induced gastrointestinal (GI) complications in patients with melanoma or genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the digestive system) may affect whether or not someone develops colitis (inflammation of the intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help doctors learn more about the effects of treatment on cells, and help doctors understand how well patients respond to treatment. Treatment with fecal transplantation may help to improve diarrhea and colitis symptoms.",[487,27,28,29,30,31,32,33,62,34,488,303,489,304,490,491,492,493,494,495,496,497,362,363,364,365,366,273,498,499,500,501,502,503,504,505,506,159,163,167,169,176,180,184],"Clinical Stage 0 Cutaneous Melanoma AJCC v8","Colitis","Malignant Genitourinary System Neoplasm","Pathologic Stage 0 Cutaneous Melanoma AJCC v8","Pathologic Stage I Cutaneous Melanoma AJCC v8","Pathologic Stage IA Cutaneous Melanoma AJCC v8","Pathologic Stage IB Cutaneous Melanoma AJCC v8","Pathologic Stage II Cutaneous Melanoma AJCC v8","Pathologic Stage IIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIC Cutaneous Melanoma AJCC v8","Stage 0 Lung Cancer AJCC v8","Stage I Lung Cancer AJCC v8","Stage IA1 Lung Cancer AJCC v8","Stage IA2 Lung Cancer AJCC v8","Stage IA3 Lung Cancer AJCC v8","Stage IB Lung Cancer AJCC v8","Stage II Lung Cancer AJCC v8","Stage IIA Lung Cancer AJCC v8","Stage IIB Lung Cancer AJCC v8",{"date":508,"type":40},"2026-03-11",{"date":510,"type":40},"2021-02-21",{"date":512,"type":21},"2026-10-31",{"name":391,"class":47},{"id":515,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":516,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":517,"targetDuration":4,"studyType":22,"phases":518,"briefSummary":25,"conditions":519,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":520,"lastUpdatePostDateStruct":521,"startDateStruct":522,"completionDateStruct":523,"leadSponsor":524,"locationsCount":48},"100416047","Inclusion Criteria:\n\n* Males or females\n* 18 to 99 years of age\n* Histologically confirmed cutaneous melanoma by historical pathology report review, clinical Stage I-III (Cohort #1), or Stage IV (Cohort #2) cutaneous melanoma\n* At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring ≥ 1 cm by digital caliper (with digital photography documentation) or ultrasound (with ultrasound image documentation)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1\n* Absolute neutrophil count (ANC) \\>= 1.5 x 10\\^3\u002Fmm\\^3 (drawn at or not more than 30 days prior to the screening visit)\n* Hemoglobin (Hgb) \\>= 9 g\u002FdL (drawn at or not more than 30 days prior to the screening visit)\n* Platelet count \\>= 100 x 10\\^3\u002Fmm\\^3 (drawn at or not more than 30 days prior to the screening visit)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 2.5 x upper limit of normal (ULN) or =\\\u003C 5 x ULN in patients with liver metastases (Cohort 2 only) (drawn at or not more than 30 days prior to the screening visit)\n* Prothrombin time =\\\u003C 1.5 x ULN (drawn at or not more than 30 days prior to the screening visit)\n* Total bilirubin =\\\u003C 1.5 x ULN (unconjugated bilirubin of \\\u003C 3 x ULN for patients with known Gilbert syndrome) (drawn at or not more than 30 days prior to the screening visit)\n* Creatinine clearance of \\>= 50 ml\u002Fmin by Cockcroft-Gault equation (drawn at or not more than 30 days prior to the screening visit)\n* Women of childbearing potential (WOCBP) must agree to use effective contraceptive methods from screening until at least:\n\n  * Cohort 1: 14 days after the surgical resection for subjects in Cohort 1\n  * Cohort 2:\n\n    * Nivolumab: 5 months after the last dose of either nivolumab or intralesional Flucelvax, whichever is later\n    * Pembrolizumab: 4 months after the last dose of either pembrolizumab or intralesional Flucelvax, whichever is later\n    * Ipilimumab: 3 months after the last dose of either ipilimumab or intralesional Flucelvax, whichever is later\n    * Relatlimab + nivolumab (marketed under the trade name Opdualag): 5 months after the last dose of either Opdualag or intralesional Flucelvax, whichever is later.\n    * Combination ipilimumab with other checkpoint inhibitor: Whichever is later:\n\n      * 3 months after the last dose of either ipilimumab or intralesional Flucelvax\n      * Above-bulleted recommendation for nivolumab or pembrolizumab\n* Non-childbearing potential is defined as a woman who meets either of the following criteria: a) postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\n* Effective contraception methods are defined as one of the following:\n\n  * True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject\n  * Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception\n  * Condoms and spermicide\n  * Diaphragm and spermicide\n  * Oral or implanted hormonal contraceptive\n  * An intra-uterine device\n* WOCBP must have a negative pregnancy test (serum or urine)\n\nExclusion Criteria:\n\n* Known allergy or intolerance to influenza vaccination\n* Subjects with condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone\u002Fequivalent) or other immunosuppressive medications within 14 days of study drug administration\n* Active, known or suspected autoimmune disease\n* Active brain metastasis or leptomeningeal metastasis\n* Diagnostic biopsy of ocular or mucosal melanoma\n* Any melanoma therapy within 6 months of enrollment; though prior surgical resection is permitted\n* Incarcerated patients\n* Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to randomization: stable and adequate CD4 counts (≥ 350 mm\\^3), and serum HIV viral load of \\\u003C 25,000 IU\u002Fml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria\n* Pregnant or lactating patients\n* Patients incapable of independently providing consent",{"count":20,"type":21},[24],[27,28,29,30,31,32,33,34,35],"2026-03-07",{"date":467,"type":40},{"date":42,"type":40},{"date":44,"type":21},{"name":46,"class":47},{"id":526,"slug":527,"hasResults":11,"nctId":528,"briefTitle":529,"officialTitle":530,"acronym":4,"eligibilityCriteria":531,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":532,"targetDuration":4,"studyType":22,"phases":534,"briefSummary":535,"conditions":536,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":539,"lastUpdatePostDateStruct":540,"startDateStruct":542,"completionDateStruct":544,"leadSponsor":545,"locationsCount":547},"100604884","phase-2-time-of-day-specified-immunotherapy-for-advanced-melanoma-the-time-trial-100604884","NCT07155317","Time-of-Day Specified Immunotherapy for Advanced Melanoma, The TIME Trial","The TIME Trial - Phase II Randomized Controlled Trial of Time-of-Day Specified Immunotherapy for Advanced Melanoma","Inclusion Criteria:\n\n* Pathologically confirmed American Joint Committee on Cancer (AJCC) 8th edition stage IV unresectable cutaneous, acral, or mucosal melanoma\n* No uveal melanoma\n* Patients with asymptomatic, non-hemorrhagic brain metastases \\\u003C 2 cm are eligible\n* No prior immunotherapy within 1 year, (serine\u002Fthreonine-protein kinase B-raf \\[BRAF\\]\u002Fmitogen-activated protein kinase \\[MEK\\] inhibitors allowed)\n* Eastern Cooperative Oncology Group (ECOG) 0-1\n* Age ≥ 18\n* Adequate organ function to receive ipilimumab\u002Fnivolumab\n\nExclusion Criteria:\n\n* Immunosuppression (\\> 10mg prednisone daily)\n* Active autoimmune disease that would preclude the administration of immunotherapy\n* Active leptomeningeal disease",{"count":533,"type":21},99,[59],"This phase II trial tests the safety and effectiveness of giving ipilimumab and nivolumab in the morning compared to other times of day in treating patients with melanoma that is stage IV or that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. While some patients have impressive outcomes with both of these drugs, over 40% of patients do not experience any clinical benefit. Studies have shown that the time of day that vaccines and other therapies are given have had an impact on response and survival. It is not known, however, whether time of day has an impact on response to immune checkpoint inhibitors, such as ipilimumab and nivolumab. Giving ipilimumab and nivolumab earlier in the day compared to later in the day may improve response to treatment and survival in patients with stage IV or unresectable melanoma.",[537,334,538,34,457,306,408,466,312,413],"Advanced Acral Melanoma","Advanced Mucosal Melanoma","2025-11-10",{"date":541,"type":40},"2025-11-12",{"date":543,"type":40},"2025-10-29",{"date":44,"type":21},{"name":546,"class":47},"Emory University",2,{"id":549,"slug":550,"hasResults":11,"nctId":551,"briefTitle":552,"officialTitle":553,"acronym":4,"eligibilityCriteria":554,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":555,"targetDuration":4,"studyType":22,"phases":557,"briefSummary":558,"conditions":559,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":561,"lastUpdatePostDateStruct":562,"startDateStruct":564,"completionDateStruct":566,"leadSponsor":568,"locationsCount":571},"100401727","phase-2-a-study-to-compare-the-administration-of-encorafenib--binimetinib--nivolumab-versus-ipilimumab--nivolumab-in-braf-v600-mutant-melanoma-with-brain-metastases-100401727","NCT04511013","A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases","A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab vs Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases","Inclusion Criteria:\n\n* Participants must have histologically and pathologically confirmed melanoma that has metastasized to the brain\n* Any primary (cutaneous, acral\u002Fmucosal, etc) or unknown origin are permitted, except that participants with uveal primary are not eligible\n* Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\n* All participants must have an magnetic resonance imaging (MRI) of the brain within 28 days prior to registration and must have central nervous system metastases with at least one measurable brain metastasis \\>= 0.5 cm in size (per modified RECIST 1.1) that has not been irradiated, or progressed (in the opinion of the treating physician) after prior radiation therapy. Participating sites MUST use MRI slice thickness of =\\\u003C 1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol. Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All central nervous system \\[CNS\\] disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form \\[RECIST 1.1\\] using RECIST 1.1.)\n* Participants may have measurable or non-measurable extracranial disease. All measurable disease must be assessed within 28 days prior to randomization; all non-measurable disease must be assessed within 42 days prior to randomization. Please note, while any extracranial disease will also be assessed and followed, participants are NOT required to have extracranial disease for randomization. NOTE: All disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). CNS disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form (RECIST 1.1) using RECIST 1.1\n* Participants may have leptomeningeal disease\n* Participants may be receiving corticosteroids for brain metastases at a dose of up to 8 mg of dexamethasone per day. The dose must not have exceeded 8 mg per day for at least 7 days prior to randomization\n* Participants must have Zubrod performance status =\\\u003C 2\n* Participants must have complete history and physical examination within 28 days prior to randomization\n* Participants must be able to swallow and retain pills\n* Hemoglobin \\>= 8.0 g\u002FdL (within 28 days prior to randomization)\n* Absolute neutrophil count \\>= 1,500\u002FmcL (within 28 days prior to randomization)\n* Platelets \\>= 75,000\u002FmcL (within 28 days prior to randomization)\n* Total bilirubin =\\\u003C 1.5 institutional upper limit of normal (ULN) (within 28 days prior to randomization)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 x institutional ULN (in participants with liver metastases =\\\u003C 5 x ULN) (within 28 days prior to randomization)\n* Creatinine =\\\u003C 2.0 institutional ULN (within 28 days prior to randomization)\n* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better\n* Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization\n* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization\n* Participants must agree to participate in image banking. Images must be submitted via the Triad System\n* Participants must be offered the opportunity to participate in specimen and blood collections\n* 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* As a part of the 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\nExclusion Criteria:\n\n* Participants must not have received prior systemic therapy for metastatic disease. Prior systemic therapy received only in the neoadjuvant and\u002For adjuvant setting (e.g., BRAF\u002FMEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon, etc.) is permitted. If patients received prior neoadjuvant\u002Fadjuvant therapy, they must have had eventual disease relapse prior to randomization\n* Participants must not have had prior radiation therapy within 7 days prior to randomization\n* Participants must not be planning to require any additional form of systemic anti-tumor therapy for melanoma while on protocol treatment\n* Participants must not be planning to use hormonal contraceptives\n* Participants must not have a serious active infection requiring systemic therapy at time of randomization in the opinion of the treating physician\n* Participants must not have active autoimmune disease that has required treatment in the past 6 months with use of biologic disease modifying agents (.e.g. infliximab, adalimumab). Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =\\\u003C 10 mg prednisone daily or equivalent (to treat auto-immune disease), or on replacement therapy (e.g., thyroxine, insulin) are eligible if deemed in the best interest of the patient by treating physician\n* Participants must not have had grade 3 or 4 immune-related adverse events on ipilimumab or nivolumab that required more than 12 weeks of immune suppression with corticosteroids\n* Participants must not have had adverse events related to encorafenib and\u002For binimetinib specifically, that required discontinuation of one or both drugs. (Please note this does not apply to other BRAF\u002FMEK inhibitor drugs.)\n* Participants must not be pregnant or nursing. Women\u002Fmen of reproductive potential must have agreed to use an effective method of contraception. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.) A woman is considered to be of \"reproductive potential\" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, \"effective contraception\" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he\u002Fshe is responsible for beginning contraceptive measures",{"count":556,"type":21},112,[59],"This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma.",[560,34,306,272,35,408,273],"Acral Lentiginous Melanoma","2025-09-04",{"date":563,"type":40},"2025-09-11",{"date":565,"type":40},"2021-01-06",{"date":567,"type":21},"2027-06-30",{"name":569,"class":570},"SWOG Cancer Research Network","NETWORK",331]