[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"stage-iv-bladder-cancer-ajcc-v8\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:stage-iv-bladder-cancer-ajcc-v8":64},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,84,120,142,169,194,219],{"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":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":72,"lastUpdatePostDateStruct":73,"startDateStruct":76,"completionDateStruct":78,"leadSponsor":80,"locationsCount":83},"100352247","phase-2-testing-the-effectiveness-of-two-immunotherapy-drugs-nivolumab-and-ipilimumab-with-one-anti-cancer-targeted-drug-cabozantinib-for-rare-genitourinary-tumors-100352247",false,"NCT03866382","Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors","A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)","Inclusion Criteria:\n\n* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:\n\n  * One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1\n  * One bone lesion on bone scan (tec99 or sodium fluoride \\[NaF\\] PET\u002FCT, CT or MRI) for the bone-only cohort.\n  * Histologically confirmed diagnosis of one of the following metastatic cohorts:\n\n    * Small cell\u002F neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded\n    * Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder\u002Furethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization \\[WHO\\] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma\n    * Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)\n    * Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly \\> or equal \\~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and\u002For rhabdoid features as well)\n    * Any penile cancer (Cohort E)\n    * Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid \\~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed\n    * Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly \\> or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly \\> or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC\n\n      * Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial\n    * Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly \\~ 50% sarcomatoid differentiation\n    * Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains\n    * Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible\n    * Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)\n    * Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder\n  * H\\&E slides from diagnostic tumor tissue for retrospective central pathology review\n* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)\n* Age \\>= 18 years\n* Patients must be able to swallow oral formulation of the tablets\n* Karnofsky performance status \\>= 80%\n* Absolute neutrophil count (ANC) \\>= 1,000\u002FmcL\n* Platelet count \\>= 75,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =\\\u003C 3.0 mg\u002FdL\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 3.0 x institutional upper limit of normal (ULN) (or =\\\u003C 5 x ULN for patients with liver metastases or Gilbert's disease)\n* Creatinine =\\\u003C 1.5 x upper limit of normal (ULN) OR creatinine clearance \\>= 40 mL\u002Fmin\u002F1.73 m\\^2 (calculated using the Chronic Kidney Disease Epidemiology \\[CKD-EPI\\] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal\n* Hemoglobin \\>= 9 g\u002FdL (transfusion of packed red blood cells \\[PRBCs\\] allowed)\n* Serum albumin \\>= 3.2 g\u002FdL\n* Lipase and amylase =\\\u003C 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis\n* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1\u002FPD-L1\u002FCTLA-4 (sequentially or in combination) are also not allowed\n* No prior treatment with any therapy on the PD-1\u002FPD-L1 axis or anti- CTLA-4\u002FCTLA-4 inhibitors with the exception of patients with \"urothelial carcinoma\" histology (cohorts D, H, J, L)\n* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable\n* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment\n* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil \\[PTU\\] or methimazole) including physiologic oral corticosteroids are eligible\n* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible\n* Women of childbearing potential must have a negative pregnancy test =\\\u003C 7 days prior to registration\n\n  * Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea \\>= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason\n* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents\n* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment\n* The patient has received no radiation therapy:\n\n  * To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy\n  * To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment\n  * To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy\n  * To any other site(s) within 2 weeks before the first dose of study treatment\n* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment\n* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment\n* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate\n* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment\n* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\\\u003C grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae\n* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility\n* No concomitant treatment with warfarin. Aspirin (up to 325 mg\u002Fday), thrombin or factor Xa inhibitors, low-dose warfarin (=\\\u003C 1 mg\u002Fday), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted\n* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors\n\n  * Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* The patient has not experienced any of the following:\n\n  * Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\n  * Hemoptysis of \\>= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment\n  * Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment\n* The patient has no tumor invading any major blood vessels\n* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible\n* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Cardiovascular disorders including:\n\n    * Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.\n    * Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \\> 150 mm Hg systolic, or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\n    * The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \\> 500 ms within 28 days before randomization. Note: if initial QTcF is found to be \\> 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =\\\u003C 500 ms, the subject meets eligibility in this regard\n    * Any history of congenital long QT syndrome\n    * Any of the following within 6 months before registration of study treatment:\n\n      * Unstable angina pectoris\n      * Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)\n      * Stroke (including transient ischemic attack \\[TIA\\], or other ischemic event)\n      * Myocardial infarction\n      * Cardiomyopathy\n  * No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\n\n    * Any of the following that have not resolved within 28 days before the first dose of study treatment:\n\n      * Active peptic ulcer disease\n      * Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome\n    * None of the following within 2 years before the first dose of study treatment:\n\n      * Abdominal fistula or genitourinary fistula\n      * Gastrointestinal perforation\n      * Bowel obstruction or gastric outlet obstruction\n      * Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment\n  * Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible\n  * No other clinically significant disorders such as:\n\n    * Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment\n    * Serious non-healing wound\u002Fulcer\u002Fbone fracture within 28 days before the first dose of study treatment\n    * History of organ or allogeneic stem cell transplant\n    * Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone \\[TSH\\], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)\n  * No history of major surgery as follows:\n\n    * Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery\n    * Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement\n    * Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery\n* No history of severe hypersensitivity reaction to any monoclonal antibody\n* No evidence of active malignancy, requiring systemic treatment within 2 years of registration\n* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study\n* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative\n* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease","ALL","18 Years",{"count":19,"type":20},314,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. 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 and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70],"Bladder Adenocarcinoma","Bladder Clear Cell Adenocarcinoma","Bladder Mixed Adenocarcinoma","Bladder Neuroendocrine Carcinoma","Bladder Small Cell Neuroendocrine Carcinoma","Bladder Squamous Cell Carcinoma","Chromophobe Renal Cell Carcinoma","Collecting Duct Carcinoma","Invasive Bladder Giant Cell Urothelial Carcinoma","Invasive Bladder Lymphoepithelioma-Like Carcinoma","Invasive Bladder Nested Urothelial Carcinoma","Invasive Bladder Plasmacytoid Urothelial Carcinoma","Invasive Bladder Sarcomatoid Urothelial Carcinoma","Invasive Bladder Urothelial Carcinoma","Kidney Medullary Carcinoma","Large Cell Neuroendocrine Carcinoma","Malignant Testicular Leydig Cell Tumor","Malignant Testicular Sertoli Cell Tumor","Metastatic Bladder Carcinoma","Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma","Metastatic Bladder Giant Cell Urothelial Carcinoma","Metastatic Bladder Large Cell Neuroendocrine Carcinoma","Metastatic Bladder Lipid-Rich Urothelial Carcinoma","Metastatic Bladder Micropapillary Urothelial Carcinoma","Metastatic Bladder Plasmacytoid Urothelial Carcinoma","Metastatic Bladder Sarcomatoid Urothelial Carcinoma","Metastatic Bladder Small Cell Neuroendocrine Carcinoma","Metastatic Bladder Squamous Cell Carcinoma","Metastatic Chromophobe Renal Cell Carcinoma","Metastatic Kidney Medullary Carcinoma","Metastatic Malignant Genitourinary System Neoplasm","Metastatic Papillary Renal Cell Carcinoma","Metastatic Penile Carcinoma","Metastatic Prostate Small Cell Neuroendocrine Carcinoma","Metastatic Sarcomatoid Renal Cell Carcinoma","Metastatic Urethral Carcinoma","Papillary Renal Cell Carcinoma","Sarcomatoid Renal Cell Carcinoma","Stage IV Bladder Cancer AJCC v8","Stage IV Penile Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IV Urethral Cancer AJCC v8","Stage IVB Prostate Cancer AJCC v8","Urachal Adenocarcinoma","Urethral Clear Cell Adenocarcinoma","RECRUITING","2026-07-01",{"date":74,"type":75},"2026-07-02","ACTUAL",{"date":77,"type":75},"2019-05-13",{"date":79,"type":20},"2027-02-28",{"name":81,"class":82},"National Cancer Institute (NCI)","NIH",581,{"id":85,"slug":86,"hasResults":11,"nctId":87,"briefTitle":88,"officialTitle":89,"acronym":4,"eligibilityCriteria":90,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":91,"targetDuration":4,"studyType":21,"phases":93,"briefSummary":95,"conditions":96,"keywords":4,"overallStatus":108,"whyStopped":4,"lastUpdateSubmitDate":109,"lastUpdatePostDateStruct":110,"startDateStruct":112,"completionDateStruct":114,"leadSponsor":116,"locationsCount":119},"100643958","phase-1-enfortumab-vedotin-pembrolizumab-and-quemliclustat-for-the-treatment-of-unresectable-locally-advanced-and-metastatic-urothelial-cancer-100643958","NCT07667335","Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer","A Phase Ib\u002FII Study to Evaluate the Safety and Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Combination With Quemliclustat in Unresectable Locally Advanced and Metastatic Urothelial Carcinoma","Inclusion Criteria:\n\n* Participants must be at least 18 years of age on the day of signing informed consent. Participant (or legally authorized representative if applicable) provides written informed consent for trial\n* Participants must have previously untreated locally advanced or metastatic bladder cancer including bladder cancer \\[stage IIIB: T1-T4N2-3M0, stage IVa: T4bAnyNM0 or AnyTAnyNM1a, and stage IVB: AnyTAnyNM1b clinical stage per American Joint Commission on Cancer (AJCC)\\] or renal pelvis or ureter cancer \\[stage IV: T4Nx-0M0, AnyTN1-2M0, AnyTAnyNM1 clinical stage per AJCC\\]. Lymph node with ≥ 15 mm short axis or biopsy-positive for carcinoma will be considered pathologically enlarged and measurable\n* Participants must have either conventional urothelial carcinoma or urothelial carcinoma variants. A review of pathology by a local expert genitourinary (GU) pathologist is required to confirm the diagnosis. Any component (%) of non-conventional urothelial noted on tumor specimen is allowed for only histologic subtypes listed below in up to 20% of participants enrolled in this study.\n\n  * Urothelial carcinoma with squamous differentiation\n  * Urothelial carcinoma with glandular differentiation\n  * Urothelial carcinoma with trophoblastic differentiation\n  * Nested urothelial carcinoma\n  * Tubular and microcystic urothelial carcinoma\n  * Micropapillary urothelial carcinoma\n  * Lymphoepithelioma-like urothelial carcinoma\n  * Plasmacytoid urothelial carcinoma\n  * Sarcomatoid urothelial carcinoma\n  * Giant cell urothelial carcinoma\n  * Lipid-rich urothelial carcinoma\n  * Clear cell (glycogen rich) urothelial carcinoma\n  * Poorly differentiated urothelial carcinoma\n  * Squamous cell neoplasms including pure squamous cell carcinomas, verrucous carcinomas and squamous cell papilloma\n* Measurable disease by RECIST v 1.1\n* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2\n* Available baseline fresh biopsy tissue sample obtained in the protocol RG1712006 though clinically indicated procedures or participants must be willing to undergo a baseline research biopsy when safe and feasible\n* Participant must have an estimated life expectancy of at least 3 months\n* Hemoglobin ≥ 9 gr\u002Fdl\n* Absolute neutrophil count: ≥ 1500\u002F µL\n* White blood cell count: ≥ 3000\u002FµL\n* Absolute lymphocyte count: ≥ 1000\u002FµL\n* Platelet count: ≥ 100.000\u002FµL (without transfusion support)\n* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2.5 x upper limit of normal (ULN)\n* Total bilirubin: ≤ 1.5 mg\u002Fdl except for patients with Gilbert's syndrome who must have a total bilirubin ≤ 3 mg\u002Fdl\n* Creatinine clearance: ≥ 30 ml\u002Fmin\u002F1.73m\\^2 by the method of Chronic Kidney Disease Epidemiology Collaboration (CKI-EPI) or ≥ 30 ml\u002Fmin by the method of 24 hour (h) clearance of creatinine calculation\n* International Normalized Ratio (INR): \\\u003C 1.5\n\nExclusion Criteria:\n\n* Participants who are receiving any other investigational agents or concurrent anticancer treatment. Participants must have adequate treatment washout period before treatment, defined as: Major surgery (≥ 4 weeks), palliative radiation therapy (≥ 1 weeks from completion of treatment if they have recovered from the acute toxic effect of radiotherapy), prior adjuvant immunotherapy (≥ 4 weeks)\n* Participants whose tumors have any % neuroendocrine or small cell histology, glandular neoplasms, urachal carcinomas, tumor of mullerian type, mesenchymal tumors or urothelial tract hematopoietic and lymphoid tumors\n* Participants considered to be medically unfit for EV-P regimen as per Investigator discretion\n* Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use\n* Participants who have experienced disease progression following neoadjuvant or adjuvant systemic therapy within 12 months prior to enrollment will not be eligible\n* Patients with Fridericia's corrected QT interval (QTcF) interval at screening of \\> 480 milliseconds.\n\n  * Note: For any QTcF \\> 480 milliseconds on initial electrocardiogram (ECG), a follow-up ECG will be performed to confirm QTcF interval prolongation and exclude the patient from this study\n* Participants with active systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma, inflammatory bowel disease). Participants with autoimmune endocrine disorders controlled by medical management (e.g. thyroid disorders, type 1 diabetes, or adrenal insufficiency) will not be excluded\n* Participants who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count \\\u003C 350 cells\u002Fmicroliter\n* Participants with known active hepatitis (i.e. Hepatitis B or C). Prior hepatitis (Hep) C infection is allowed as long as polymerase chain reaction (PCR) test is negative\n* Participants with clinically inactive brain metastases may be included. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment\n* Participants with new or progressive brain metastases (less or equal of 1 cm of larger diameter) are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the participant and the investigator favors participation in the clinical trial. Patients with leptomeningeal disease will be excluded\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator\n* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy of assessment of the investigational regimen are eligible for this trial\n* Woman of childbearing potential with positive serum pregnancy test within 72 hours prior to enrollment. Active lactation is an exclusion criterion",{"count":92,"type":20},27,[94,23],"PHASE1","This phase Ib\u002FII trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), 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 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. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and\u002For effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.",[97,98,99,46,100,101,102,64,103,104,105,106,107],"Locally Advanced Bladder Urothelial Carcinoma","Locally Advanced Renal Pelvis Urothelial Carcinoma","Locally Advanced Ureter Urothelial Carcinoma","Metastatic Renal Pelvis Urothelial Carcinoma","Metastatic Ureter Urothelial Carcinoma","Stage IIIB Bladder Cancer AJCC v8","Stage IV Renal Pelvis Cancer AJCC v8","Stage IV Ureter Cancer AJCC v8","Unresectable Bladder Urothelial Carcinoma","Unresectable Renal Pelvis Urothelial Carcinoma","Unresectable Ureter Urothelial Carcinoma","NOT_YET_RECRUITING","2026-06-18",{"date":111,"type":75},"2026-06-25",{"date":113,"type":20},"2026-12-01",{"date":115,"type":20},"2029-07-16",{"name":117,"class":118},"Fred Hutchinson Cancer Center","OTHER",1,{"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":130,"conditions":131,"keywords":4,"overallStatus":108,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":138,"leadSponsor":140,"locationsCount":119},"100641890","phase-1-consolidative-therapy-after-ev--pembrolizumab-in-muscle-invasive-bladder-cancer-reinforce-trial-100641890","NCT07579195","Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial","Consolidative Radiation Therapy or Cystectomy After Initial Favorable Response Succeeding Enfortumab Vedotin Plus Pembrolizumab (REINFORCE)--- A Phase I\u002FII Pilot Feasibility Trial","Inclusion Criteria:\n\n* Age \\>= 18 at the time of screening\n* Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants\n* Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis\n* Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro\n* If M1 after completion of EV + pembro, patients need to have =\\\u003C 5 sites of metastasis and all sites of metastasis should be extracranial\n\n  * Note: when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastatic lesions, etc). Five or fewer sites of metastasis applies after the completion of EV + pembro, not at initial diagnosis\n* Be a candidate for consolidative radiation therapy (RT) to the pelvis (if indicated) or cystectomy (if indicated), and all sites of metastasis are amenable to RT\n* Life expectancy \\> 6 months\n* Eastern Cooperative Oncology Group (ECOG) performance 0-2\n* Absolute neutrophil count (ANC) \\>= 1500 \u002FmcL (within 180 days of trial registration)\n* Platelets \\>= 100,000\u002FmcL (within 180 days of trial registration)\n* Hemoglobin \\> 9 g\u002FdL (within 180 days of trial registration)\n* Creatinine =\\\u003C 1.5 x upper limit of normal (ULN) OR \\>= 60 mL\u002Fmin (within 180 days of trial registration)\n* Total bilirubin =\\\u003C 1.5 ULN OR direct bilirubin =\\\u003C ULN if total bilirubin \\> 1.5 x ULN (within 180 days of trial registration)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 x ULN OR \\\u003C 5 x ULN if patient has live metastasis (within 180 days of trial registration)\n* Albumin \\>= 2.5 g\u002FdL (within 180 days of trial registration)\n* International normalized ratio (INR) or prothrombin time (PT) =\\\u003C 1.5 x ULN unless on anticoagulation therapy, in which case PT or partial thromboplastin time (PTT) should be in the therapeutic range (within 180 days of trial registration)\n* PTT =\\\u003C 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range (within 180 days of trial registration)\n* Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception during, and for at least 90 days after the end of radiation therapy. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours of treatment initiation\n* HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial\n\nExclusion Criteria:\n\n* Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation\n* Intracranial metastasis\n* Any small cell component, or predominant (\\> 50%) sarcomatoid or plasmacytoid histology\n* Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator\n* Genetic conditions that increase sensitivity to radiation, such as Fanconi syndrome, ataxia telangiectasia, and Nijmegen breakage syndrome\n* Active human immunodeficiency virus (HIV) not adequately controlled, active hepatitis B (e.g., hepatitis B virus surface antigen \\[HBsAg\\] reactive) or hepatitis C (e.g., hepatitis C virus \\[HCV\\] ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected)\n* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Any other medical condition that may interfere with trial therapy delivery",{"count":128,"type":20},12,[94,23],"This phase I\u002FII clinical trial is evaluating a novel treatment strategy for patients with advanced bladder cancer that is unresectable, has spread to nearby lymph nodes or a limited number of distant sites (oligometastatic disease), and has responded to initial treatment with enfortumab vedotin and pembrolizumab. Although this combination has significantly improved outcomes compared to traditional chemotherapy, many patients are left with residual cancer in the bladder or other sites, and there is currently no established standard approach for managing this remaining disease or determining the optimal duration of systemic therapy. Prolonged treatment can lead to cumulative side effects and negatively impact quality of life.\n\nThis study investigates whether adding consolidative treatment-such as radiation therapy to the bladder and metastatic sites or surgical removal of the bladder (radical cystectomy)-can safely eliminate residual disease and delay cancer progression. Radiation therapy uses high-energy x-rays to precisely target and destroy cancer cells while minimizing exposure to surrounding normal tissues. In selected patients, surgery may be used to remove remaining tumor in the bladder. Targeted radiation techniques, such as stereotactic body radiation therapy (SBRT), may also be used to treat small metastatic sites. This approach may allow for safe discontinuation of systemic therapy, potentially reducing long-term treatment-related side effects.\n\nA key component of this trial is the integration of biomarker testing using circulating tumor DNA (ctDNA) from blood and urine tumor DNA (utDNA). These tests detect small amounts of tumor-derived genetic material and may help identify patients most likely to benefit from consolidative treatment, as well as guide decisions about ongoing therapy. By combining response to systemic therapy with personalized local treatment and biomarker-driven monitoring, this study aims to improve cancer control, reduce complications from untreated local disease, and inform future treatment strategies for patients with advanced bladder cancer.",[132,133,64],"Muscle Invasive Bladder Carcinoma","Stage III Bladder Cancer AJCC v8","2026-06-17",{"date":136,"type":75},"2026-06-22",{"date":72,"type":20},{"date":139,"type":20},"2029-12-31",{"name":141,"class":118},"University of Washington",{"id":143,"slug":144,"hasResults":11,"nctId":145,"briefTitle":146,"officialTitle":147,"acronym":4,"eligibilityCriteria":148,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":21,"phases":151,"briefSummary":152,"conditions":153,"keywords":157,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":159,"lastUpdatePostDateStruct":160,"startDateStruct":162,"completionDateStruct":164,"leadSponsor":166,"locationsCount":168},"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","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)",{"count":150,"type":20},64,[23],"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.",[154,155,64,156],"Metastatic Bladder Urothelial Carcinoma","Metastatic Malignant Solid Neoplasm","MTAP Deletion",[158],"KMT2D (gene)\u002FMLL4 (protein) or KDM6A (gene)\u002FUTX (protein) or MTAP loss of function mutations","2026-06-10",{"date":161,"type":75},"2026-06-12",{"date":163,"type":75},"2024-11-27",{"date":165,"type":20},"2030-05-10",{"name":167,"class":118},"Northwestern University",2,{"id":170,"slug":171,"hasResults":11,"nctId":172,"briefTitle":173,"officialTitle":174,"acronym":4,"eligibilityCriteria":175,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":176,"targetDuration":4,"studyType":21,"phases":178,"briefSummary":180,"conditions":181,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":185,"lastUpdatePostDateStruct":186,"startDateStruct":188,"completionDateStruct":190,"leadSponsor":192,"locationsCount":119},"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":177,"type":20},75,[179],"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.",[97,182,154,183,133,64,184],"Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma","Metastatic Renal Pelvis and Ureter Urothelial Carcinoma","Stage IV Renal Pelvis and Ureter Cancer AJCC v8","2026-02-10",{"date":187,"type":75},"2026-02-12",{"date":189,"type":75},"2025-01-08",{"date":191,"type":20},"2034-12-31",{"name":193,"class":118},"Mayo Clinic",{"id":195,"slug":196,"hasResults":11,"nctId":197,"briefTitle":198,"officialTitle":199,"acronym":4,"eligibilityCriteria":200,"healthyVolunteers":201,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":202,"targetDuration":4,"studyType":21,"phases":204,"briefSummary":206,"conditions":207,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":210,"lastUpdatePostDateStruct":211,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":119},"100547926","an-education-and-navigation-support-tool-to-improve-participation-in-care-coordination-among-patients-with-locally-advanced-metastatic-and-unresectable-bladder-cancer-and-their-caregivers-100547926","NCT06414317","An Education and Navigation Support Tool to Improve Participation in Care Coordination Among Patients With Locally Advanced, Metastatic and Unresectable Bladder Cancer and Their Caregivers","A Comprehensive Education and Navigational Support Program for Advanced Bladder Cancer","Inclusion Criteria:\n\n* PATIENTS: Age ≥ 18 years\n* PATIENTS: Metastatic or locally advanced, unresectable bladder cancer\n* PATIENTS: Receiving or planning to receive systemic therapy for bladder cancer at Roswell Park Comprehensive Cancer Center (RPCCC)\n* PATIENTS: Subjects can be enrolled any time from initial diagnosis of advanced disease to within 8 weeks after initiation of first-line systemic therapy for advanced bladder cancer\n* PATIENTS: Able to speak, understand, read, and write English\n* CAREGIVERS: Age ≥ 18 years\n* CAREGIVERS: Only caregivers of enrolled patients will be included in the study\n* CAREGIVERS: Should be able to speak, understand, read, and write English\n* CAREGIVERS: Caregivers will be enrolled in the study during the same time window as for patient enrollment (from initial visit to within 8 weeks of patients starting frontline therapy)\n\nExclusion Criteria:\n\n* PATIENTS: Not receiving any form of systemic therapy for bladder cancer due to Eastern Cooperative Oncology Group (ECOG) performance status (PS) \\> 3, co-morbidities, or inadequate organ function\n* PATIENTS: Predominantly small cell histology\n* PATIENTS: Adults with impaired decision-making capacity, assessed by the study team to be unable to participate in ENST-based education and surveys\n* PATIENTS: Pregnant women\n* CAREGIVERS: Cognitively impaired adults\u002Fadults with impaired decision-making capacity\n* CAREGIVERS: Individuals who are not yet adults (infants, children, teenagers)",true,{"count":203,"type":20},160,[205],"NA","This clinical trial evaluates the impact of an education and navigation support tool (ENST) on patient and caregiver participation in care coordination for bladder cancer that has spread to nearby tissue or lymph nodes (locally advanced), to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Patients with advanced bladder cancer tend to be older, have multiple medical conditions and often have poor access to health care. An ENST may be an effective method to improve participation in treatment decision-making and care planning among patients with locally advanced, metastatic and unresectable bladder cancer and their caregivers.",[208,44,133,64,209],"Locally Advanced Bladder Carcinoma","Unresectable Bladder Carcinoma","2026-01-27",{"date":212,"type":75},"2026-01-29",{"date":214,"type":75},"2024-01-12",{"date":216,"type":20},"2027-03-31",{"name":218,"class":118},"Roswell Park Cancer Institute",{"id":220,"slug":221,"hasResults":11,"nctId":222,"briefTitle":223,"officialTitle":224,"acronym":4,"eligibilityCriteria":225,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":226,"targetDuration":4,"studyType":21,"phases":228,"briefSummary":229,"conditions":230,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":234,"lastUpdatePostDateStruct":235,"startDateStruct":237,"completionDateStruct":239,"leadSponsor":241,"locationsCount":243},"100497386","phase-2-enfortumab-vedotin-plus-pembrolizumab-for-the-treatment-of-locally-advanced-or-metastatic-bladder-cancer-of-variant-histology-100497386","NCT05756569","Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology","Phase II Single-Arm Study of Enfortumab Vedotin (EV) Plus Pembrolizumab in the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology","Inclusion Criteria:\n\n* Male or Female\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%)\n* Metastatic disease or unresectable locally advanced disease\n* Histologically documented variant histology (nested, microcytic, micropapillary, lymphoepithelioma-like, plasmacytoid, giant cell, poorly differentiated, lipid-rich, clear cell, sarcomatoid) bladder cancer and non-urothelial bladder cancer of epithelial origin including squamous cell carcinoma and adenocarcinoma (urachal and non-urachal). Variant histology tumors and non-urothelial tumors of ureter, urethra, urachus, or renal pelvis are included. Patients with mixed cell type are eligible if the predominant histology (over 50%) is variant or non-urothelial. All histological classifications will follow the 2016 WHO Classifications.\n* Untreated or having received any number of lines of prior therapy\n* Tumor tissue samples must be available for submission prior to initiation of study treatment. If not, agree to undergo biopsy\n* Patients must have measurable disease as defined by RECIST criteria 1.1 as at least one lesion that can be accurately measured in at least one dimension (longest diameter of \\>= 10 mm for non-nodal lesions or short axis of \\>= 15 mm for nodal lesions) on CT scan, MRI\n* Patients must have adequate organ and marrow function, within 28 days of cycle 1 day 1, at the discretion of the investigator\n* The effects of study drugs on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy\n* FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Additionally, FCBP and male subjects should use effective contraception for 6 months after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male subjects must not donate sperm and female subjects must not donate ova from screening to 6 months after the last dose\n* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer \\>= 4 weeks before the start of study therapy\n* Life expectancy \\> 12 weeks as determined by the Investigator\n* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions\n* Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation\n\nExclusion Criteria:\n\n* The neuroendocrine histology (small cell and large cell carcinomas) and non-epithelial bladder tumors (e.g. bladder sarcoma, carcinosarcoma, paraganglioma, melanoma, primary lymphoma, and lymphoepithelioma-like carcinoma) are excluded.\n* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier \\[i.e. ongoing clinically significant toxicity (grade 2 or higher with the exception of alopecia) associated with prior treatment\\]\n* Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study\n* Patients with ongoing sensory or motor neuropathy grade \\>= 2\n* Prior treatment or enrollment in a study with EV or PD1\u002FPD-L1 immune checkpoint inhibitor (including maintenance therapy)\n* Known uncontrolled diabetes mellitus with glycated hemoglobin (HbA1c) \\>= 8% or HbA1c 7% to \\\u003C 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained\n* Active central nervous system (CNS) metastases\n* Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for localized prostate cancer, definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months\n* Currently receiving systemic antimicrobial treatment for active infection or high dose steroids (\\> 10mg of prednisone or equivalent)\n* A FCBP who has a positive urine pregnancy test at baseline or within 72 hours prior to receiving first study dose. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Breastfeeding females\n* History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), known hepatitis B (defined as hepatitis B surface antigen \\[HBsAg\\] reactive), known active hepatitis C virus (defined as HCV ribonucleic acid \\[mRNA\\] \\[qualitative\\] is detected) or tuberculosis\n* History of active keratitis or corneal ulcerations\n* History of allogenic tissue\u002Fsolid organ transplant\n* Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 6 months prior to first dose of EV\u002Fpembrolizumab\n* Other uncontrolled current illness including, but not limited to, cardiac arrhythmia or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements",{"count":227,"type":20},25,[23],"This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have 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. 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. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.",[31,208,231,232,233,44,133,64,209,69,26],"Malignant Renal Pelvis Neoplasm","Malignant Ureter Neoplasm","Malignant Urethral Neoplasm","2025-07-24",{"date":236,"type":75},"2025-07-28",{"date":238,"type":75},"2023-09-26",{"date":240,"type":20},"2027-12-16",{"name":242,"class":118},"Emory University",4]