BCG+MM Trial Adding mitomycin to BCG as adjuvant intravesical therapy for high-risk, non–muscle-invasive bladder cancer: a randomised phase 3 trial

INTERVENTION: Trade Name: Mitomycin‐C Product Name: Mitomycin‐C Pharmaceutical Form: Concentrate for intravesical solution INN or Proposed INN: Mitomycin‐C Concentration unit: mg milligram(s) Trade Name: BCG Product Name: BCG Pharmaceutical Form: Concentrate for intravesical solution INN or Proposed INN: Bacille Calmette‐Guerin Concentration unit: mg milligram(s) CONDITION: High grade non muscle invasive bladder cancer Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To assess whether patients treated with a combination of BCG and MM have fewer recurrences and live longer than patients treated with BCG alone. Primary end point(s): Disease free survival Secondary Objective: To compare: 1) Activity (clear cystoscopy at 3 months) 2) Time to recurrence 3) Time to progression (recurrence of higher grade or stage cancer) 4) Safety (adverse events) 5) Health‐related quality of life (HRQL) 6) Overall survival time (death from any cause) 7) Feasibility (compliance with intravesical therapy) 8) Marginal resource use (e.g. number of GP visits, number of outpatient and emergency department visits, number of inpatient admissions and the number of days admitted) Timepoint(s) of evaluation of this end point: Evaluation timepoints of thus end point would be at time of identification of recurrent bladder cancer, time of death (if occurs) SECONDARY OUTCOME: Secondary end point(s): 1) Activity (clear cystoscopy at 3 months) 2) Time to recurrence 3) Time to progression (recurrence of higher grade or stage cancer) 4) Safety (adverse events) 5) Health‐related quality of life (HRQL) 6) Overall survival time (death from any cause) 7) Feasibility (compliance with intravesical therapy) 8) Marginal resource use (e.g. number of GP visits, number of outpatient and emergency department visits, number of inpatient admissions and the number of days admitted) INCLUSION CRITERIA: 1. Males or females with confirmed high grade pTa or stage pT1 (any grade) non‐muscle invasive bladder cancer on initial or re‐resection histology (concurrent carcinoma in situ is allowed). 2. Age = 18 yrs 3. No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may either be the initial TURBT at which the primary tumour was completely resected, or a planned second cystoscopy and/ or re‐resection done within 8 weeks of the initial TURBT. 4. ECOG Performance Status of 0‐2 5. Adequate bone marrow, renal and liver function 6. Study treatment both planned and able to start within 4 weeks of randomisation 7. Is willing to complete HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision 8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments 9. Signed, written informed c