NCT04506554

A Study of Risk Enabled Therapy After Neoadjuvant Immunochemotherapy for Bladder Cancer

A Phase II Trial of Risk Enabled Therapy After Neoadjuvant Immunochemotherapy for Bladder Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 81 (actual)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Neoadjuvant accelerated methotrexate/vinblastine/adriamycin/cisplatin (AMVAC) in combination with nivolumab is under evaluation for the treatment of muscle invasive bladder cancer (MIBC). Patients with pre-specified tumor mutations and complete clinical response with neoadjuvant therapy will preserve their bladders and go on active surveillance.

Detailed description

Muscle invasive bladder cancer (MIBC) constitutes 20-25% of all cases with 5 year survival estimated at 45% regardless of treatment.1-4 Although neoadjuvant cisplatin-based chemotherapy (NAC) followed by a radical cystectomy or cystoprostatectomy with a lymph node dissection is the preferred treatment choice for MIBC in the United States, there are several drawbacks and challenges with this approach. Patients must be fit to undergo a surgical intervention. Grade 2 through 5 complications have been documented in 53% of patients undergoing cystectomy at a tertiary care center, and the surgical mortality rate is 1.5%.5, 6 Furthermore, urinary diversion commonly requires an ileal conduit and an external appliance, impacting patient's quality of life. By incorporating neoadjuvant nivolumab with AMVAC, our goal in RETAIN-2 is to increase the number of patients who would be eligible for bladder preservation while maintaining the long-term oncologic outcomes. Nivolumab, an anti-PD1 therapy, is FDA approved for treatment of metastatic urothelial carcinoma post platinum-based chemotherapy.20 Recently, neoadjuvant pembrolizumab (anti-PD1) and atezolizumab (anti-PDL1) was tested in MIBC in the PURE-01 and ABACUS studies, and a pT0 rate of 38.6% and 29%, respectively, was achieved.21, 22 Additionally, recent work by Kim et al. presented at AACR 2019 demonstrated that AMVAC induces gene signatures in luminal tumors and may have a synergistic response with immunotherapy. Given the impressive activity of both AMVAC and nivolumab in the neoadjuvant setting, in this study the investigators hypothesize that using the combination of neoadjuvant nivolumab and AMVAC will lead to higher cT0 rate and metastasis-free survival at 2 years. At the same time by using the risk adapted strategy, a select group of patients will be able to preserve their bladders and significantly improve their quality-of-life.

Conditions

• Muscle-Invasive Bladder Carcinoma

Interventions

Type	Name	Description
DRUG	AMVAC + Nivolumab	Nivolumab 240mg will be administered intravenously for 3 doses - on days 1, 15 and 29. AMVAC will be dosed intravenously every 2 weeks for 3 doses on days 1, 15 and 29 with Neulasta or equivalent. Standard AMVAC dose is as follows: methotrexate 30mg/m2, vinblastine 3mg/m2, doxorubicin 30mg/m2, and cisplatin 70mg/m2.

Timeline

• Start date: 2020-12-01
• Primary completion: 2026-05-01
• Completion: 2028-11-01
• First posted: 2020-08-10
• Last updated: 2025-07-04

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study