Clinical Trial: A Single-Arm, Prospective, Phase II Study on the Safety and Efficacy of Consolidative Surgery after Disease Control with Enfortumab Vedotin and Pembrolizumab in Stage IV Upper Urinary Tract Urothelial Carcinoma (Japan)

Tokyo, Oct. 19 -- UMIN Clinical Trials Registry (UMIN-CTR) received information related to the study (UMIN000063281) titled 'A study of the safety and effectiveness of surgery after enfortumab vedotin plus pembrolizumab for stage IV upper urinary tract cancer' on Oct. 19.

Study Type: Interventional

Study Design: Basic Design - Single arm Randomization - Non-randomized Blinding - Open -no one is blinded Control - Uncontrolled

Primary Sponsor: Institute - another

Condition: Condition - Stage IV upper urinary tract urothelial carcinoma (renal pelvic or ureteral cancer) Classification by malignancy - Malignancy Genomic information - NO

Objective: Narrative objectives1 - The primary objective of this study is to prospectively evaluate the safety and technical feasibility of consolidative surgery, consisting of radical nephroureterectomy or segmental ureterectomy, for the primary tumor in patients with stage IV upper urinary tract urothelial carcinoma who have achieved disease control with enfortumab vedotin plus pembrolizumab (EVP). Oncological outcomes of this treatment strategy will also be explored in comparison with historical data from patients treated with EVP alone. Basic objectives2 - Safety

Intervention: Interventions/Control_1 - Patients with stage IV upper urinary tract urothelial carcinoma who have received enfortumab vedotin plus pembrolizumab (EVP) as standard clinical care and achieved CR, PR, or SD according to RECIST v1.1 will undergo centralized multidisciplinary team (MDT) review for surgical eligibility.

Patients judged eligible for surgery by the central MDT will undergo consolidative surgery for the primary tumor, consisting of radical nephroureterectomy or segmental ureterectomy.

Surgery will generally be performed 4 to 8 weeks after the last dose of EVP. The interval may be extended up to 12 weeks for medical reasons, including recovery from adverse events. Open, laparoscopic, or robot-assisted approaches are permitted. The decision to perform lymph node dissection and its extent will be left to the treating surgeon. Postoperative treatment is not specified by the protocol and will be determined by the treating physician as part of standard clinical care.

Eligibility: Age-lower limit - 20 years-old <= Age-upper limit - Not applicable Gender - Male and Female Key inclusion criteria - 1. Age 20 years or older at the time of informed consent; both sexes are eligible. 2. Histologically diagnosed upper urinary tract urothelial carcinoma of the renal pelvis or ureter. Tissue biopsy is required in principle; if biopsy is difficult, positive urinary cytology together with imaging findings consistent with upper urinary tract urothelial carcinoma is acceptable. 3. Stage IV disease at initial diagnosis: cT4, cN1-2, or conditionally eligible cM1. 4. Treatment with enfortumab vedotin plus pembrolizumab (EVP) with CR, PR, or SD confirmed according to RECIST v1.1. At least 3 cycles are required in principle; if treatment is interrupted for unavoidable reasons including adverse events, enrollment is permitted if eligibility criteria are met at 9 weeks (63 days) after the first dose. 5. For cM1 disease, metastatic lesions must either achieve CR with EVP or disappear after local treatment such as metastasectomy or radiotherapy, with clinically no evidence of disease maintained for at least 3 months. 6. ECOG Performance Status 0-1. 7. Written informed consent provided by the patient. 8. Consolidative surgery judged feasible by the central multidisciplinary team. Key exclusion criteria - 1. Unresolved grade 3 or higher adverse events related to EVP treatment. 2. Direct invasion of adjacent organs or major blood vessels on imaging such that surgical resection is considered technically infeasible or unsafe. 3. Active synchronous or metachronous malignancy, except malignancies considered adequately controlled and unlikely to affect outcome assessment, including non-muscle-invasive bladder cancer, early prostate cancer, or completely resected basal cell carcinoma of the skin. 4. Pregnant women or women who may be pregnant. 5. Breastfeeding women. 6. Any other condition considered inappropriate for study participation by the investigator. Target Size - 42

Recruitment Status: Recruitment status - Preinitiation Date of protocol fixation - 2026 Year 09 Month 16 Day Date of IRB - 2026 Year 10 Month 08 Day Anticipated trial start date - 2026 Year 10 Month 30 Day Last follow-up date - 2031 Year 03 Month 31 Day

To know more, visit https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072433

Disclaimer: Curated by HT Syndication.