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) — ASN Events
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  3. 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)

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) (#267)

Venu Chalasani 1 , Shomik Sengupta 2 , Martin Stockler 3 , Steve McCombie 4 , Cynthia Hawks 4 , Laurence Krieger 5 , Paul Anderson 4 6 , Jeremy Grummet 7 , Andrew J Mitterdorfer 8 , Conrad Bishop 9 , Emma Beardsley 10 , Andrew Martin 3 , Nicola Lawrence 3 , Nicole Wong 3 , Howard Chan 3 , Mariya Pysarenko 3 , Matthew Harper 11 , Manish Patel 12 , Akil Hamid 4 , Ian Davis 13 , Dickon Hayne 4 6 , and on behalf of ANZUP 14
  1. North Shore Hospital, Sydney, NSW, Australia
  2. Austin Health, Melbourne, Victoria, Australia
  3. NHMRC Clinical Trials Group, Camperdown, NSW, Australia
  4. Fiona Stanley Hospital, Perth, Western Australia, Australia
  5. Northern Cancer Institute, Sydney, New South Wales, Australia
  6. University of Western Australia, Perth, WA, Australia
  7. Alfred Hospital, Melbourne, Victoria, Australia
  8. Concord Repatriation General Hospital , Sydney, NSW, Australia
  9. Footscray Hospital, Melbourne, Victoria , Australia
  10. Frankston Hospital, Peninsula Health, Frankston, Victoria, Australia
  11. Monash Medical Centre, Melbourne, Victoria, Australia
  12. Westmead Hospital, University of Sydney, Sydney, New South Of Wales, Australia
  13. Monash University Eastern Health Clinical School, Melbourne, Victoria , Australia
  14. Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia

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: 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. 

Participants: 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.

Acknowledgements  to Omegapharm and Merck Sharp & Dohme for providing study drug.

ANZUP is supported by Cancer Australia and CI NSW

ANZCTR#:  ACTRN12613000513718

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