Randomised phase 3 trial of the addition of mitomycin to bcg as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer(anzup 1301).

Background: Instillation of Bacillus Calmette-Guerin (BCG) into the urinary bladder (intravesical administration) decreases rates of disease recurrence after transurethral resection (TUR) of high risk, non-muscle invasive bladder cancer (NMIBC), but over 30% of people recur despite optimal adjuvant intravesical BCG. Our meta-analysis and pilot study, suggest outcomes can improve by using an adjuvant intravesical regimen including Mitomycin and BCG. Aim(s): To determine the efficacy and safety of Mitomycin in addition to BCG in patients with NMIBC Trial Design: An open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial. Primary endpoint is disease free survival (evidence of transitional cell carcinoma [TCC]) or death. Secondary endpoints are: activity (clear cystoscopy at 3 months), time to recurrence of TCC, time to progression, safety, HRQOL, overall survival, feasibility, marginal resource use. Tertiary objective is to undertake exploratory biomarker studies to predict clinical outcomes. 500 participants will provide an 85% power to detect a 10% improvement in DFS rate at 2 years from 70% on BCG alone to 80% on BCG and Mitomycin (HR 0.63) at a significance level of 0.05, allowing for 10% non-compliance. Participant(s): Adults with resected, high-risk NMIBC (high grade Ta or any grade T1) suitable for intravesical chemotherapy. Regimen: Randomisation 1:1 to intravesical BCG alone (standard): induction (weekly x 6), followed by Maintenance (monthly x 10) OR Intravesical BCG + Mitomycin (experimental): Induction (weekly x 9) followed by Maintenance (monthly x 9). Assessments: Cystoscopy, ratings of HRQL and resource use at baseline and months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48 and 60. Clinical assessments include adverse events assessment weekly during induction, then monthly before each maintenance chemotherapy instillation. Status: As of August 2015, 9 sites open in Australia with 46 participants recruited.