title: BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301).
abstract: BACKGROUND
  Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration.
  
  
  METHODS
  The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use.
  
  
  BACKGROUND
  This trial is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000513718 ).
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. dickon.hayne@uwa.edu.au.|School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. dickon.hayne@uwa.edu.au.|Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. dickon.hayne@uwa.edu.au.
authors.forename: Dickon
authors.initials: D
authors.lastname: Hayne
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. martin.stockler@sydney.edu.au.|NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. martin.stockler@sydney.edu.au.
authors.forename: Martin
authors.initials: M
authors.lastname: Stockler
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. stevemccombie@ymail.com.|School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. stevemccombie@ymail.com.|Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. stevemccombie@ymail.com.
authors.forename: Steve P
authors.initials: SP
authors.lastname: McCombie
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. venu.chalasani@sydney.edu.au.|NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. venu.chalasani@sydney.edu.au.|Department of Urology, Hornsby Ku-Ring-Gai Hospital, Sydney, NSW, 2077, Australia. venu.chalasani@sydney.edu.au.
authors.forename: Venu
authors.initials: V
authors.lastname: Chalasani
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. anne.long@ctc.usyd.edu.au.|NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. anne.long@ctc.usyd.edu.au.
authors.forename: Anne
authors.initials: A
authors.lastname: Long
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. andrew.martin@ctc.usyd.edu.au.|NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. andrew.martin@ctc.usyd.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Martin
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. senguptaurology@gmail.com.|Department of Urology, Austin Health, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.|Austin Department of Surgery, University of Melbourne, Melbourne, VIC, 3010, Australia. senguptaurology@gmail.com.|Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.
authors.forename: Shomik
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. ian.davis@monash.edu.|Monash University Eastern Health Clinical School, Box Hill, Melbourne, VIC, 3128, Australia. ian.davis@monash.edu.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
mesh_terms: D000283:Administration, Intravesical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000628:therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D016685:Mitomycin