NCT03609216

Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations

A Phase II Study of Gemcitabine Plus Cisplatin Chemotherapy in Patients With Muscle-invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 237 (actual)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed description

PRIMARY OBJECTIVES: I. To determine the 3-year event free survival, defined as the proportion of patients without invasive or metastatic recurrence following definitive gemcitabine hydrochloride (gemcitabine) and cisplatin (standard or dose-dense) chemotherapy in those patients whose pre-treatment transurethral resection of bladder tumor (TURBT) tumors harbor deleterious DDR gene alterations and who achieve \< cT1 response to chemotherapy. SECONDARY OBJECTIVES: I. To determine the clinical response rate (\< cT1) for patients harboring deleterious DDR gene alterations following dose dense gemcitabine and cisplatin. II. To determine the bladder-intact and overall survival for DDR-altered patients with \< cT1. III. For DDR gene altered patients who elect radical cystectomy despite \< cT1, to determine the pT0 rate in this patient population. IV. To determine the pathologic response rate at cystectomy and 3-year recurrence-free and overall survival for patients without DDR mutations who are registered onto this trial. V. To assess the local treatment burden (Bacillus Calmette-Guerin \[BCG\] therapy, resection of non-invasive disease, checkpoint blockade) over time in the bladder-sparing group. VI. To determine the bladder-intact disease-free survival in patients who elect to undergo chemoradiation therapy in the DDR mutant group and the DDR wild-type group. OUTLINE: Participants receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants are then assigned to 1 of 2 arms. ARM I: Participants with DDR gene alteration and disease stage \< cT1 undergo bladder sparing. ARM II: Participants with DDR gene alteration and disease stage \>= cT1 or participants without DDR gene alteration undergo radical cystectomy or chemoradiotherapy. After completion of study treatment, participants are followed up for 5 years.

Conditions

• Infiltrating Bladder Urothelial Carcinoma
• Stage II Bladder Urothelial Carcinoma
• Stage III Bladder Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Gemcitabine Hydrochloride	Given IV
DRUG	Cisplatin	Given IV
BIOLOGICAL	Pegfilgrastim	Given SC
PROCEDURE	Conventional Surgery	Undergo bladder sparing
PROCEDURE	Radical Cystectomy	Undergo radical cystectomy
OTHER	Chemoradiotherapy	Undergo chemoradiotherapy

Timeline

• Start date: 2018-12-10
• Primary completion: 2027-02-01
• Completion: 2029-02-01
• First posted: 2018-08-01
• Last updated: 2026-04-13

Locations

424 sites across 1 country: United States

Regulatory

• FDA-regulated drug study