[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"locally-advanced-bladder-urothelial-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:locally-advanced-bladder-urothelial-carcinoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,53],{"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":25,"conditions":26,"keywords":4,"overallStatus":40,"whyStopped":4,"lastUpdateSubmitDate":41,"lastUpdatePostDateStruct":42,"startDateStruct":45,"completionDateStruct":47,"leadSponsor":49,"locationsCount":52},"100643958","phase-1-enfortumab-vedotin-pembrolizumab-and-quemliclustat-for-the-treatment-of-unresectable-locally-advanced-and-metastatic-urothelial-cancer-100643958",false,"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","ALL","18 Years",{"count":19,"type":20},27,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","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.",[27,28,29,30,31,32,33,34,35,36,37,38,39],"Locally Advanced Bladder Urothelial Carcinoma","Locally Advanced Renal Pelvis Urothelial Carcinoma","Locally Advanced Ureter Urothelial Carcinoma","Metastatic Bladder Giant Cell Urothelial Carcinoma","Metastatic Renal Pelvis Urothelial Carcinoma","Metastatic Ureter Urothelial Carcinoma","Stage IIIB Bladder Cancer AJCC v8","Stage IV 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":43,"type":44},"2026-06-25","ACTUAL",{"date":46,"type":20},"2026-12-01",{"date":48,"type":20},"2029-07-16",{"name":50,"class":51},"Fred Hutchinson Cancer Center","OTHER",1,{"id":54,"slug":55,"hasResults":11,"nctId":56,"briefTitle":57,"officialTitle":58,"acronym":4,"eligibilityCriteria":59,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":60,"targetDuration":4,"studyType":21,"phases":62,"briefSummary":64,"conditions":65,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":72,"lastUpdatePostDateStruct":73,"startDateStruct":75,"completionDateStruct":77,"leadSponsor":79,"locationsCount":52},"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":61,"type":20},75,[63],"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.",[27,66,67,68,69,34,70],"Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma","Metastatic Bladder Urothelial Carcinoma","Metastatic Renal Pelvis and Ureter Urothelial Carcinoma","Stage III Bladder Cancer AJCC v8","Stage IV Renal Pelvis and Ureter Cancer AJCC v8","RECRUITING","2026-02-10",{"date":74,"type":44},"2026-02-12",{"date":76,"type":44},"2025-01-08",{"date":78,"type":20},"2034-12-31",{"name":80,"class":51},"Mayo Clinic"]