CCTG BL13 a randomized phase II trial assessing trimodality therapy with or without adjuvant durvalumab to treat patients with muscle-invasive bladder cancer (NCT03768570).

Abstract

TPS4619 Background: Immunotherapy improves outcomes in the advanced (Bellmunt 2019; Powles 2020) as well as in the adjuvant setting post cystectomy (Bajorin 2021) for muscle invasive bladder cancer (MIBC) patients. Trimodality treatment (TMT) consisting of transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy (CRT) may be considered an alternative to radical cystectomy in MIBC. The role of radiotherapy and chemotherapy as immune system stimulants provides a rationale to evaluate the anticancer activity of checkpoint inhibitors in this patient population. Durvalumab, an anti PDL1 inhibitor, administered after CRT leads to improvement in PFS and OS in patients with locally advanced NSCLC, which further supports the rationale for this study (Antonia 2017, 2018). We hypothesized that durvalumab will improve outcomes in patients with MIBC when administered in the adjuvant setting after completion of trimodality therapy. Methods: CCTG BL13 is a Canadian Cancer Trials Group, randomized phase II trial in patients with stage T2-T4a N0M0, urothelial carcinoma treated with TURBT followed by radiotherapy with concurrent chemotherapy. Treatment arms consist of durvalumab 1500 mg IV q 4 weeks for 12 months versus surveillance. The primary objective: to compare disease free survival (DFS) between arms (RECIST 1.1, investigator assessed). Secondary endpoints include a non muscle-invasive bladder cancer recurrence rate (< T2); locoregional control rate; overall survival; bladder intact DFS, patterns of disease recurrence; metastasis free survival; safety; quality of life ; economics evaluation. A pilot sub study (BL13F) has been activated and will evaluate the feasibility of electronic real-time patient self-reporting of immunotherapy related symptomatic adverse events using the SYMPTOM-IQ Tool on the uMotif Mobile Health Application (APP). Statistical Design: Randomization 1:1 balanced for stratification factors: ECOG PS; neoadjuvant chemotherapy; radiation field extent; T2 vs T3/T4; centre. Assuming a 2-year DFS rate 65% for patients on the control arm and estimated 12% improvement in the 2-year DFS rate (65% to 77% (HR 0.61)) with 80% power using a 1-sided 10% level test requires a sample size of 190 including 5% drop out rate. Conduct to Date: Study activation Dec 2018. Enrollment as of January 31 2022: 49. The DSMC reviewed and recommended trial continuation in November 2021. Clinical trial information: NCT03768570.