Adding mitomycin to Bacillus Calmette-Guérin as adjuvant intravesical therapy for high-risk, nonmuscle-invasive urothelial bladder cancer (BCGMM; ANZUP 1301).

TPS602 Background: Adjuvant intravesical bacillus Calmette-Guérin (BCG) decreases disease recurrence and progression in people with high-risk, non-muscle invasive urothelial bladder cancer (NMIBC), however recurrence occurs in 30% despite optimal therapy. Recent meta-analyses evaluating addition of intravesical mitomycin (MM) to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Good quality randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will be the largest study to date evaluating this approach in people with high-risk NMIBC. Methods: This open-label phase 3 trial aims to randomize 500 participants, stratified by stage, site of disease, and presence of carcinoma in-situ, to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG + MM weekly x9 then monthly x9). This study is powered to detect a 10% improvement in 2-year disease free survival (DFS) at 5% level of significance with 85% power. Stage 1 of this study, designed to recruit 130 patients to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, has completed enrolment and successfully established feasibility of this trial protocol. Stage 2, aiming for a further 370 patients, will inform on additional endpoints including differences in DFS, time to recurrence and progression, overall survival, and potential predictive biomarkers, is estimated to complete accrual in December 2020. Successful treatment completion, defined as 75% or more of planned treatment doses, has been achieved in 76% of patients treated in the experimental arm of Stage 1, compared to 60% in those allocated BCG alone. Clinical trial information: NCT02948543.