Clinical Trial

. 2015 May 27:15:432.

doi: 10.1186/s12885-015-1431-6.

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)

Dickon Hayne^{1

2

3}, Martin Stockler^{4

5}, Steve P McCombie^{6

7

8}, Venu Chalasani^{9

10

11}, Anne Long^{12

13}, Andrew Martin^{14

15}, Shomik Sengupta^{16

17

18

19}, Ian D Davis^{20

21}

Affiliations

¹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. dickon.hayne@uwa.edu.au.
² School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. dickon.hayne@uwa.edu.au.
³ Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. dickon.hayne@uwa.edu.au.
⁴ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. martin.stockler@sydney.edu.au.
⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. martin.stockler@sydney.edu.au.
⁶ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. stevemccombie@ymail.com.
⁷ School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. stevemccombie@ymail.com.
⁸ Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. stevemccombie@ymail.com.
⁹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. venu.chalasani@sydney.edu.au.
¹⁰ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. venu.chalasani@sydney.edu.au.
¹¹ Department of Urology, Hornsby Ku-Ring-Gai Hospital, Sydney, NSW, 2077, Australia. venu.chalasani@sydney.edu.au.
¹² Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. anne.long@ctc.usyd.edu.au.
¹³ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. anne.long@ctc.usyd.edu.au.
¹⁴ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. andrew.martin@ctc.usyd.edu.au.
¹⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. andrew.martin@ctc.usyd.edu.au.
¹⁶ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. senguptaurology@gmail.com.
¹⁷ Department of Urology, Austin Health, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.
¹⁸ Austin Department of Surgery, University of Melbourne, Melbourne, VIC, 3010, Australia. senguptaurology@gmail.com.
¹⁹ Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.
²⁰ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. ian.davis@monash.edu.
²¹ Monash University Eastern Health Clinical School, Box Hill, Melbourne, VIC, 3128, Australia. ian.davis@monash.edu.

PMID: 26014129
PMCID: PMC4445809
DOI: 10.1186/s12885-015-1431-6

Clinical Trial

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)

Dickon Hayne et al. BMC Cancer. 2015.

. 2015 May 27:15:432.

doi: 10.1186/s12885-015-1431-6.

Authors

Affiliations

¹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. dickon.hayne@uwa.edu.au.
² School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. dickon.hayne@uwa.edu.au.
³ Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. dickon.hayne@uwa.edu.au.
⁴ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. martin.stockler@sydney.edu.au.
⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. martin.stockler@sydney.edu.au.
⁶ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. stevemccombie@ymail.com.
⁷ School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia. stevemccombie@ymail.com.
⁸ Fiona Stanley Hospital Urology (proudly supported by WAURO), Murdoch, WA, 6150, Australia. stevemccombie@ymail.com.
⁹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. venu.chalasani@sydney.edu.au.
¹⁰ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. venu.chalasani@sydney.edu.au.
¹¹ Department of Urology, Hornsby Ku-Ring-Gai Hospital, Sydney, NSW, 2077, Australia. venu.chalasani@sydney.edu.au.
¹² Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. anne.long@ctc.usyd.edu.au.
¹³ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. anne.long@ctc.usyd.edu.au.
¹⁴ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. andrew.martin@ctc.usyd.edu.au.
¹⁵ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2050, Australia. andrew.martin@ctc.usyd.edu.au.
¹⁶ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. senguptaurology@gmail.com.
¹⁷ Department of Urology, Austin Health, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.
¹⁸ Austin Department of Surgery, University of Melbourne, Melbourne, VIC, 3010, Australia. senguptaurology@gmail.com.
¹⁹ Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, VIC, 3084, Australia. senguptaurology@gmail.com.
²⁰ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia. ian.davis@monash.edu.
²¹ Monash University Eastern Health Clinical School, Box Hill, Melbourne, VIC, 3128, Australia. ian.davis@monash.edu.

PMID: 26014129
PMCID: PMC4445809
DOI: 10.1186/s12885-015-1431-6

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 and design: 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.

Trial registration: This trial is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000513718 ).

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Figures

**Fig. 1**
Pilot data on median (a) I-PSS and (b) cystitis scores

**Fig. 2**
Summary of standard (Arm A) and experimental (Arm B) treatment regimens (displays treatment administration in terms of nominal weeks, and not calendar weeks, and thus accommodates treatment delays)

See this image and copyright information in PMC

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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)

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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)

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