[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-bladder-urothelial-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-bladder-urothelial-carcinoma":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,45,73,120],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":30,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100564533","phase-2-pemetrexed-response-in-relation-to-tumor-alterations-of-gene-status-for-the-treatment-of-patients-with-metastatic-urothelial-bladder-cancer-and-other-solid-tumors-100564533",false,"NCT06630416","Pemetrexed Response in Relation to Tumor Alterations of Gene Status for the Treatment of Patients With Metastatic Urothelial Bladder Cancer and Other Solid Tumors","A Phase II Trial to Evaluate Pemetrexed Response in Relation to Tumor Alterations of Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma and Other Solid Tumors","Inclusion Criteria:\n\n* Patients must have pathologically or cytologically confirmed metastatic urothelial bladder carcinoma (Arm A) or other metastatic\u002Flocally-advanced solid malignancy (Arm B) and MLL4- protein (KMT2D-gene) or UTX-protein (KDM6A-gene) or MTAP loss of function mutation including but not limited to SNVs that cause truncation, CNVs, and indels confirmed by next generation sequencing or immunohistochemistry techniques.\n* Patients must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), measured preferably by computed tomography (CT) scan.\n* Patients who have received any prior neoadjuvant or systemic chemotherapy are eligible.\n\n  * Notes:\n\n    * Patients must have progressive disease despite two prior lines of therapy in the metastatic setting or locally advanced setting unless the patient was not suitable for an approved second line regimen due to intolerance or another clinical factor;\n    * Treatment cannot have included prior pemetrexed. Any prior intravesical therapy, or immunotherapy is allowed. At least 3 weeks (21 days) wash-out period since prior chemotherapy or radiation therapy or targeted agent is required.\n* Patients must be aged ≥ 18 years.\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Patients must have adequate organ and bone marrow function as defined:\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL (growth factor allowed and can be added at the discretion of the treating oncologist)\n* Hemoglobin (Hgb) ≥ 8.5 g\u002FdL (without the need for transfusion within the previous one week)\n* Platelets (PLT) ≥ 100,000\u002FmL (without the need for platelet transfusion within the previous one week)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg\u002FdL\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Creatinine clearance ≥ 45 mL\u002Fmin\u002F1.73 m\\^2 using the standard Cockcroft and Gault formula\n* Patients must have the ability to comply with the administration of supplemental therapies including folic acid, vitamin B12 and steroids as directed by study team and as per standard of care and institutional standards and practice for pemetrexed use.\n* Patients must be able swallow oral medication or not have problems\u002Fdiseases that affect absorption or oral medication.\n* Patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it was previously done as part of the patient's health care, it should be documented for eligibility.\n* Patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Please note this lab is not a requirement for eligibility, however, if the lab has been completed previously as part of the patient's health care, then it should be documented for eligibility.\n* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with a known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Please note this lab is not a requirement for eligibility, however if it was previously done as part of the patient's health care, it should be documented for eligibility.\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n* Pemetrexed is known to be teratogenic. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 180 days following completion of pemetrexed therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 180 days after completion of administration\n\n  * Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria:\n\n    * Has not undergone a hysterectomy or bilateral oophorectomy\n    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n* POCBP must have a negative pregnancy test prior to registration on study.\n* The ability to interrupt nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin at higher dose (\\> 1.3 g per day) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.\n* Patients must be able to understand and voluntarily sign a written informed consent and willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion Criteria:\n\n* Patients who received prior pemetrexed containing chemotherapy.\n* Patients who have had chemotherapy or radiotherapy ≤ 21 days (prior to planned treatment start date). For palliative radiation, 5 day wash out is sufficient.\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia, neuropathy and other non-significant adverse events deemed not clinically significant by the treating investigator, adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).\n* Patients who are receiving any other investigational agents. A 21 day wash out period will be required after discontinuation of an investigational agent prior to first day of study treatment.\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed.\n* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:\n\n  * Ongoing or active infection requiring systemic treatment\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.\n\n  * Note: To be eligible for this trial, patients should be class 2B or better\n* Patients with presence of third space fluid which cannot be controlled by drainage\n\n  * Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy\n* Has received the final dose of any of the following treatments\u002F procedures with the specified minimum intervals before first dose of study drug:\n\n  * Focal radiation therapy - 7 days\n  * Surgery with general anesthesia - 7 days\n  * Surgery with local anesthesia - 3 days\n  * For palliative radiation - 5 days\n* Patients of child bearing (POCB) potential who are pregnant or nursing.\n\n  * Note: Registration of patients is completed in Northwestern Oncology Trial Information System (NOTIS)","ALL","18 Years",{"count":19,"type":20},64,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) with mutations that result in a loss of function in the MLL4-protein\u002FKMT2D-gene or UTX-protein\u002FKDM6A-gene or MTAP enzyme. Loss of function due to a genetic mutation means a gene's activity may be reduced or eliminated. Mutations that result in a loss of function in the MLL4-protein or KMT2D-gene are found in 9.96% of all cancers including bladder carcinoma patients, esophageal squamous cell carcinoma and esophageal adenocarcinoma patients. In addition, mutations that result in a loss of function in the UTX-protein or KDM6A-gene are found in approximately 5% of all tumors, including bladder cancers, endometrial cancer, and esophagogastric cancer amongst many other tumor types. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill tumor cells. Giving pemetrexed may increase response in patients with metastatic urothelial bladder cancer and other solid tumors with the loss of function in the MLL4-protein\u002FKMT2D-gene or UTX-protein\u002FKDM6A-gene or MTAP enzyme.",[26,27,28,29],"Metastatic Bladder Urothelial Carcinoma","Metastatic Malignant Solid Neoplasm","Stage IV Bladder Cancer AJCC v8","MTAP Deletion",[31],"KMT2D (gene)\u002FMLL4 (protein) or KDM6A (gene)\u002FUTX (protein) or MTAP loss of function mutations","RECRUITING","2026-06-10",{"date":35,"type":36},"2026-06-12","ACTUAL",{"date":38,"type":36},"2024-11-27",{"date":40,"type":20},"2030-05-10",{"name":42,"class":43},"Northwestern University","OTHER",2,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":21,"phases":55,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":72},"100599697","phase-2-therapeutic-plasma-exchange-with-enfortumab-vedotin-and-pembrolizumab-for-treatment-of-bladder-cancers-100599697","NCT07087860","Therapeutic Plasma Exchange With Enfortumab Vedotin and Pembrolizumab for Treatment of Bladder Cancers","MC220503 Randomized Phase II Rescuing Cancer Immunotherapy With Plasma Exchange in Bladder Cancer 1 (ReCIPE-B1)","RECIPE-B1","Inclusion Criteria:\n\n* Age ≥ 18 years\n* GROPUS A and B (reCIPE-B1): Histologically proven urothelial carcinoma \\[American Joint Committee on Cancer (AJCC) 2017\\] of the bladder (BCa) or upper urothelial tract (UTUC), that has progressed despite enfortumab vedotin and pembrolizumab treatment\n\n  * NOTE: Primary or secondary progression are allowed, therapies are not required to be concurrent or immediately antecedent to enrollment)\n* COHORT C (CAKE ReCIPE): Histologically proven urothelial carcinoma (AJCC 2017) of the bladder (BCa) or upper urothelial tract (UTUC), that has progressed despite ADC AND is otherwise not a candidate for Groups A and B\n\n  * NOTE: Patients in Groups A and B who have progressed on that treatment are candidates for this cohort. Such patients must be re-consented and re- enrolled\n* Measurable disease per RECIST version (v)1.1\n* Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2\n* Hemoglobin \\> 7.0 g\u002FdL (obtained ≤ 30 days prior to registration)\n* Platelet count ≥ 75,000\u002Fmm\\^3 (obtained ≤ 30 days prior to registration)\n* Alanine aminotransferase (ALT) OR aspartate transaminase (AST) ≤ 3.5 x upper limit of normal (ULN) OR total bilirubin ≤ 3 x ULN OR direct bilirubin ≤ 3 x ULN (obtained ≤ 30 days prior to registration)\n* Estimated glomerular filtration rate (GFR) ≥ 15 ml\u002Fmin (obtained ≤ 30 days prior to registration)\n* Negative pregnancy test ≤ 8 days prior to registration, for persons of childbearing potential only\n* Provide written informed consent\n* Ability to complete questionnaire(s) by themselves or with assistance\n* Willingness to undergo treatment as assigned (group A: TPE + EV\u002Fpembro; OR group B: next line standard of care; OR Cohort C TPE + ADC)\n* Willingness to provide mandatory blood and fluid specimens for correlative research\n* Willingness to provide tissue specimens for correlative research\n* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)\n\nExclusion Criteria:\n\n* Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception\n* Any of the following histologic variants\u002Fdivergent differentiation: Any amount of neuroendocrine or signet ring cell features\n* Active malignancies (i.e., progressing or requiring treatment change ≤ 24 months before registration) other than the disease being treated under study\n\n  * EXCEPTIONS:\n\n    * Skin cancer (melanoma or non-melanoma) that is considered completely cured\n    * Non-invasive cervical cancer that is considered completely cured\n    * Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ considered to have a very low risk of recurrence\n    * Localized prostate cancer (T1c\u002FT2N0M0):\n\n      * Gleason score 6, treated by either surgery or ablation ≤ 24 months prior to registration or untreated and under active surveillance\n      * Gleason score 3+4 that has been treated (may include surgery or ablation) ≤ 24 months prior to registration and considered to have a very low risk of recurrence (i.e., cT1c or pT2 on prostatectomy specimen)\n* History of uncontrolled cardiovascular disease including any of the following ≤ 6 months prior to registration:\n\n  * Significant cardiovascular disease \\[New York Heart Association (NYHA) class ≥ III\\], symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cerebrovascular accident, or transient ischemic attack\n  * Psychiatric illness\u002Fsocial situations (e.g., substance abuse) that would limit compliance with study requirements\n* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participants (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments",{"count":54,"type":20},70,[23],"This phase II trial compares therapeutic plasma exchange followed by enfortumab vedotin and pembrolizumab to standard of care next-line therapy for the treatment of patients with bladder or upper urinary tract cancers that have spread from where they first started (primary site) to other places in the body (metastatic) and that have not responded to previous treatment (refractory). TPE is a process that slowly removes a patient's blood through an intravenous or central line. The blood is sent through a machine that separates the plasma (the liquid part of blood) from other blood components (red cells, white cells, platelets). The plasma is then removed. The remaining blood components are combined with replacement fluid and returned to the patient's bloodstream through the intravenous or central line. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. 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. Treatment with enfortumab vedotin and pembrolizumab is already approved by the Food and Drug Administration for the treatment of bladder cancer, but TPE is not. Combining TPE with enfortumab vedotin and pembrolizumab may work better than standard of care options for treating metastatic and refractory bladder and urinary tract cancers. This study also evaluates the effect of TPE with standard of care antibody drug conjugates (ADCs) in treating patients with refractory metastatic bladder cancer. ADC therapy is treatment with a monoclonal antibody linked to a chemotherapy drug. It is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, and delivers chemotherapy to kill them. Giving TPE with standard of care ADC therapy may be effective in treating patients with refractory metastatic bladder cancer.",[26,58,59,60,61,62],"Metastatic Renal Pelvis and Ureter Urothelial Carcinoma","Refractory Bladder Urothelial Carcinoma","Refractory Renal Pelvis and Ureter Urothelial Carcinoma","Stage IV Bladder Cancer AJCC v7","Stage IV Renal Pelvis and Ureter Cancer AJCC v7","2026-05-06",{"date":65,"type":36},"2026-05-08",{"date":67,"type":36},"2025-08-01",{"date":69,"type":20},"2028-08-07",{"name":71,"class":43},"Mayo Clinic",1,{"id":74,"slug":75,"hasResults":11,"nctId":76,"briefTitle":77,"officialTitle":78,"acronym":79,"eligibilityCriteria":80,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":83,"phases":4,"briefSummary":84,"conditions":85,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":119},"100542959","immune-checkpoint-inhibitor-response-in-solid-tumors-using-a-live-tumor-diagnostic-platform-100542959","NCT06349642","Immune Checkpoint Inhibitor Response in Solid Tumors Using a Live Tumor Diagnostic Platform","Observational Basket Trial to Collect Tissue to Develop and Train a Live Tumor Diagnostic Platform","ELEPHAS-04","Inclusion Criteria:\n\nSubjects must meet one of the following criteria:\n\n* Subjects suspected of or diagnosed with the following Stage IV\u002Fmetastatic or recurrent malignancies:\n\n  * Lung: Non-small Cell Lung Cancer (NSCLC)\n  * Skin: Cutaneous Malignancy, excluding Uveal Melanoma\n  * Esophageal Cancer\n  * Cervical Cancer\n  * Endometrial Cancer\n  * Colon Cancer: Mismatch repair deficient (dMMR) CRC only\n  * All solid tumors with high tumor mutation burden (TMB)\n  * All solid tumors that are microsatellite instability high (MSI-H)\n  * All mismatch repair deficient (dMMR) solid tumors\n  * Liver Cancer\n  * Any solid tumor with measurable disease that is eligible for pure ICI therapy or that the clinician plans to treat with immune checkpoint inhibitor (ICI) therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate laboratory developed tests (LDTs) that, per clinician, render the patient eligible for ICI therapy, either frontline or a later line.\n\nOR\n\n* Subjects suspected of or diagnosed with the following Stage III per provider discretion or IV\u002Fmetastatic malignancies:\n\n  * Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)\n  * Bladder: Urothelial Carcinoma (UC)\n  * Any solid tumor with measurable disease that is eligible for pure ICI therapy or that the clinician plans to treat with ICI therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line\n\nOR\n\n* Patients who will be receiving neoadjuvant CPI for the following resectable early-stage malignancies:\n\n  * Breast Cancer: Triple negative breast cancer (TNBC)\n  * Lung: Non-small cell lung cancer (NSCLC)\n\n    * NOTE: Patients with suspected NSCLC who would be eligible for neoadjuvant checkpoint inhibitor (CPI) are eligible to enroll per provider discretion\n  * Any solid tumor that is eligible for pure ICI therapy or that the clinician plans to treat with ICI therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line\n* LOCALLY ADVANCED\u002FMETASTATIC PATIENTS: Measurable disease as defined per protocol NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible.\n* NEOADJUVANT PATIENTS: Subjects must be eligible based on investigator discretion to receive approved CPI therapy.\n* Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy.\n* Subjects who are Stage I, II, or III and have progressed to metastatic cannot have received any anti-cancer treatment for at least 2 - 4 weeks (depending upon the washout period of prior anti-cancer treatment) prior to biopsy as per the agents used.\n* ECOG Performance Status (PS) 0, 1 or 2.\n* Negative pregnancy test done ≤7 days prior to enrollment, for persons of childbearing potential only\n* Female subjects must not be pregnant or breastfeeding and must use appropriate methods of contraception when applicable.\n* Subjects must be clinically able, at investigator discretion, and willing to undergo either:\n\n  * additional biopsy passes during their standard of care biopsy, OR\n  * a biopsy for research only, if applicable.\n  * NOTE: These additional biopsies may either be collected from the primary tumor or a metastatic site amenable to biopsies per the clinician.\n* Subjects with a known secondary cancer diagnosis are eligible to participate if participation does not interfere with systemic anti-cancer standard of care treatment for suspected primary diagnosis.\n* Provide written informed consent\n\nExclusion Criteria:\n\n* Pregnant women because this study involves a greater than minimal risk procedure (biopsy)\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 for the biopsy\n* Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy\n\n  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * ongoing or active infection\n  * psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Subjects who are enrolled or plan to be enrolled in a blinded cancer therapeutic treatment trial",{"count":82,"type":20},324,"OBSERVATIONAL","This study is being done to collect tissue samples to test how accurately a tumor response platform, Elephas, can predict clinical response across multiple types of immunotherapies, chemoimmunotherapy and tumor types.",[86,26,87,88,89,90,91,92,93,94,27,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110],"Early Stage Triple-Negative Breast Carcinoma","Metastatic Cervical Carcinoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Colorectal Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Esophageal Carcinoma","Metastatic Liver Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Skin Neoplasm","Resectable Lung Non-Small Cell Carcinoma","Early Stage Lung Non-Small Cell Carcinoma","Resectable Malignant Solid Neoplasm","Resectable Triple-Negative Breast Carcinoma","Stage III Renal Cell Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Recurrent Cervical Carcinoma","Recurrent Colorectal Carcinoma","Recurrent Endometrial Carcinoma","Recurrent Esophageal Carcinoma","Recurrent Liver Carcinoma","Recurrent Lung Non-Small Cell Carcinoma","Recurrent Malignant Skin Neoplasm","Recurrent Malignant Solid Neoplasm","2026-03-11",{"date":113,"type":36},"2026-03-12",{"date":115,"type":36},"2024-04-24",{"date":117,"type":20},"2027-05",{"name":71,"class":43},3,{"id":121,"slug":122,"hasResults":11,"nctId":123,"briefTitle":124,"officialTitle":125,"acronym":4,"eligibilityCriteria":126,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":127,"targetDuration":4,"studyType":21,"phases":129,"briefSummary":131,"conditions":132,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":138,"startDateStruct":140,"completionDateStruct":142,"leadSponsor":144,"locationsCount":72},"100574808","phase-4-enfortumab-vedotin-and-pembrolizumab-with-cystectomy-andor-ureterectomy-for-locally-advanced-or-metastatic-bladder-and-upper-urothelial-tract-cancer-cast-ai-trial-100574808","NCT06764095","Enfortumab Vedotin and Pembrolizumab With Cystectomy and\u002For Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial","CAST-AI: Cystectomy After Systemic Therapy With ADC and Immunotherapy","Inclusion Criteria:\n\n* 18 years of age or older at the time of informed consent\n* Histologically proven urothelial carcinoma \\[American Joint Committee on Cancer (AJCC) 2017\\] of the bladder (BCa) or upper urothelial tract (UTUC), N+ and\u002For M+. Initial diagnosis must be within 90 days of planned date for treatment initiation\n\n  * The following variant histologic subtypes are permitted in any amount\n\n    * Urothelial with squamous differentiation\n    * Urothelial with sarcomatoid differentiation\n  * Mixed variant histologic subtypes are permitted if urothelial differentiation is predominant (e.g., \\\u003C 50% variant histologic subtype)\n* Willing to undergo cytoreductive cystectomy (CC) or ureterectomy (U) and deemed clinically a surgical candidate (presuming good response) by the attending urologist\n* Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2\n* Hemoglobin ≥ 8.0 g\u002FdL (obtained ≤ 28 days prior to registration)\n* Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 (obtained ≤ 28 days prior to registration)\n* Platelet count ≥ 80,000\u002Fmm\\^3 (obtained ≤ 28 days prior to registration)\n* Alanine aminotransferase (ALT) OR aspartate transaminase (AST) ≤ 3.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)\n* Total bilirubin ≤ 3 x ULN OR direct bilirubin ≤ 3 x ULN (obtained ≤ 28 days prior to registration)\n* Estimated glomerular filtration rate ≥ 15 ml\u002Fmin (obtained ≤ 28 days prior to registration)\n* Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted, but interval between this treatment and study enrollment must exceed 24 months\n* All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 grade \\\u003C 2 prior to registration\n* Must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study and agree to store samples when applicable\n* Ability to complete questionnaire(s) by themselves or with assistance\n* Willingness to provide mandatory blood specimens for correlative research\n* Willingness to provide tissue specimens for correlative research\n* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)\n\nExclusion Criteria:\n\n* The following histologic variants\u002Fdivergent differentiation are excluded from trial participation:\n\n  * Presence of urothelial carcinoma with histologic variants comprising \\> 50% of histology\n  * Any amount: neuroendocrine, micropapillary, or signet ring cell features\n* Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time (excluding intravesicular therapies)\n* Known active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:\n\n  * Skin cancer (non-melanoma or melanoma) that is considered completely cured\n  * Non-invasive cervical cancer treated that is considered completely cured\n  * Breast cancer:\n\n    * Adequately treated lobular carcinoma in situ or ductal carcinoma in situ considered to have a very low risk of recurrence\n  * Localized prostate cancer (T1c\u002FT2N0M0):\n\n    * Gleason score 6, treated by either surgery or ablation within the last 24 months or untreated and under active surveillance\n    * Gleason score 3+4 that has been treated (may include surgery or ablation) within the last 24 months and considered to have a very low risk of recurrence (i.e., cT1c or pT2 on prostatectomy specimen)\n* Received prior systemic chemotherapy or targeted small molecule therapy (excluding hormonal therapy) within 2 years prior to starting study treatment\n* History of uncontrolled adrenal insufficiency\n* History of uncontrolled cardiovascular disease including any of the following in the preceding 6 months: unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive New York Heart Association class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; pulmonary embolism or other venous thromboembolism\n* Known active tuberculosis\n* Is receiving immunosuppression for an allogeneic tissue\u002Fsolid organ transplant\n* Participants with an active autoimmune disease requiring systemic treatment. Participants with autoimmune disorders not requiring systemic treatment (eg, skin conditions such as vitiligo or alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll\n* Known clinically significant liver disease that precludes participant treatment regimens prescribed on the study (including, but not limited to active viral, alcoholic, or other autoimmune hepatitis, cirrhosis, or inherited liver disease)\n* Known human immunodeficiency virus (HIV) infection, unless the participant has been on a stable antiretroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of \\> 350 in the last 6 months\n* Known active hepatitis B or C infection \\[however, participants with history of hepatitis C infection but normal hepatitis C virus polymerase chain reaction test and participants with hepatitis B with positive hepatitis B surface antigen (HBsAg) antibody are allowed\\]\n* Known urinary tract infection (UTI), defined as a symptomatic infection with a positive urine culture with a bacterial count of ≥ 10\\^5 colony forming units (CFU)\u002FmL in urine voided from women, or \\> 104 CFU\u002FmL in urine voided from men, or in straight catheter urine from women. Symptoms may include dysuria, urgency, frequency, and\u002For systemic symptoms such as fever, chills, elevated white blood cell, and\u002For abdominal\u002Fflank pain. Participants free from symptoms for 7 days with no culture evidence of ≥ 10\\^5 CFUs may be eligible\n* Known active, uncontrolled urogenital bacterial, viral or fungal infections, including UTI. Skin\u002Fnail fungal infections are not exclusionary. Participants with active shingles (varicella zoster infection) will be excluded from the study\n* Evidence of interstitial lung disease or active non-infectious pneumonitis\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Participants who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation\n* Known history of impaired wound healing capacity defined as skin\u002Fdecubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions\n* Pelvic radiotherapy administered at any time\n* Received a live virus vaccine within 30 days of planned start of study treatment\n* Active autoimmune disease that has required systemic treatment in the past 2 years\n* Active infection requiring systemic intravenous therapy within 30 days prior to planned treatment initiation\n* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways\n* Participants with a history of grade ≥ 3 toxic effects when using anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-6 agents are excluded\n* Participants still recovering from toxicity of prior anticancer therapy which was received more than 24 months prior to enrollment (except toxicities which are not clinically significant such as alopecia, skin discoloration)\n* Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses \\> 10 mg\u002Fday of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF alpha blockers. Use of immunosuppressive medications for the management of immune related adverse events, infusion related reactions, or in participants with contrast allergies is acceptable. Use of inhaled, topical, and intranasal corticosteroids are permitted\n* Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune mediated thrombocytopenia or anemia) are excluded\n* Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment\n* Participants who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before registration \\[transurethral resection of bladder tumor (TURBT) is not considered major surgery\\]. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate\n* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception\n* Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participants (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments\n* The participant is unable to comply with the requirements of this protocol, including any factors that are likely to affect the participant's return for scheduled visits and follow-up",{"count":128,"type":20},75,[130],"PHASE4","This phase IV trial tests the impact of standard of care enfortumab vedotin and pembrolizumab followed by removal of all or part of the bladder (cytoreductive cystectomy) and\u002For removal of all or part of the tube that carriers urine from the kidneys to the bladder (ureterectomy) on outcomes in patients with bladder and upper urothelial tract that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving standard of care enfortumab vedotin and pembrolizumab followed by cytoreductive cystectomy and\u002For ureterectomy (CC\u002FU) may improve outcomes in patients with locally advanced or metastatic bladder or upper urothelial tract cancer.",[133,134,26,58,135,28,136],"Locally Advanced Bladder Urothelial Carcinoma","Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma","Stage III Bladder Cancer AJCC v8","Stage IV Renal Pelvis and Ureter Cancer AJCC v8","2026-02-10",{"date":139,"type":36},"2026-02-12",{"date":141,"type":36},"2025-01-08",{"date":143,"type":20},"2034-12-31",{"name":71,"class":43}]