Status:
Recruiting
Clinicaltrials.gov identifier:
Sponsor:
National Cancer Institute/Alliance
Enrollment:
271
Study Design:
This trials enrolls patients with histologically confirmed MIBC (cT2-T4aN0/xM0) disease on TURBT and sequences their tumors with MSK-IMPACT. All patients are treated with dose-dense gemcitabine and cisplatin (undergoing current amendment to be given at investigator’s discretion with six cycles over 12 weeks or 4 cycles over 12 weeks). Patients with deleterious alterations in at least one or more DDR genes can undergo repeat TURBT and if residual disease is cT0 or CIS, patients can undergo bladder-sparing (observed without additional therapy). Patients with cT1 disease or greater will go on to receive chemoradiation or radical cystectomy. Patients without deleterious alterations in DDR genes will have an option to either undergo chemoradiation or radical cystectomy.
Rationale:
Bladder preservation is an important topic to address in patients witn muscle invasive bladder cancer (MIBC). Some prospective series have demonstrated a subset of patients with MIBC who have experienced a complete response to neoadjuvant chemotherapy and who have remained free of disease. Patients whose tumors harbor deleterious DNA Damage Response (DDR) Gene Alterations have a greater chance of responding to cisplatin based chemotherapy and obtaining a complete response, perhaps avoiding cystectomy. This trial prospectively tests this hypothesis in patients with MIBC.
Endpoints:
The primary endpoint is 3-year event-free survival in the bladder-sparing group which is defined as the proportion of patients without invasive or metastatic recurrence following definitive dose-dense gemcitabine and cisplatin chemotherapy in those patients whose pre-treatment TURBT tumors harbored DDR gene alterations and who achieved <cT1 response to chemotherapy. The secondary endpoint is the pT0 and <pT2 rate in all patients who ultimately undergo a radical cystecdtomy.
Comments:
This trial is very similar to a trial being conducted at Fox Chase Cancer Center and both test the premise that DDR alterations (genes such as ERCC2, ERCC5, BRCA1, BRCA2, RAD51C, ATR, ATM, FANCC, and RECQL4) in MIBC can predict for patients that might be exceptional responders to chemotherapy. We eagerly await this intelligent strategy for selection of patients for bladder-sparing. Questions still linger regarding the development of MIBC and the potential aggressiveness of any resulting NMIBC in the patients that undergo bladder sparing and have a NMIBC recurrence.
Results:
This trial is still accruing and has enrolled at least 91 patients to date.
