Adding Mitomycin to BCG as Adjuvant Intravesical Therapy for High-risk Non-Muscle-invasive Bladder Cancer
BCG+MM
Adding Mitomycin to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial
2 other identifiers
interventional
501
2 countries
17
Brief Summary
Open label, randomised phase 3 trial of the addition of Mitomycin to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer. The study aim is to compare disease-free survival between treatment arms: BCG alone versus Mitomycin in addition to BCG.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2013
Longer than P75 for phase_3
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2013
CompletedFirst Submitted
Initial submission to the registry
August 1, 2016
CompletedFirst Posted
Study publicly available on registry
October 28, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2024
CompletedJune 18, 2023
June 1, 2023
11.4 years
August 1, 2016
June 14, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Disease free survival (death or recurrence)
Measured from the date of randomisation until the date of disease recurrence, upper tract disease is first evident, or the date of death, or until the date last known to be alive and without disease recurrence. Assessed via cystoscopy.
Up to 5 years
Secondary Outcomes (8)
Activity (Clear cystoscopy at 3 months)
At 3 months after patient randomised
Time to recurrence (recurrence)
Up to 5 years
Time to progression (disease progression)
Up to 5 years
Safety (Adverse events graded according to CTC AE V4.0)
Measured before day 1 of each instillation during treatment.
Health-Related Quality of Life
Up to 5 years from the date of randomisation
- +3 more secondary outcomes
Other Outcomes (1)
Exploratory Tissue Biomarker Investigation
Baseline
Study Arms (2)
Treatment (Arm B):Intravesical BCG + MM
EXPERIMENTALInduction (weekly x 9); and followed by Maintenance (monthly x 9) beginning 3 months after randomisation. Dosage of Bacillus of Calmette-Guerin (BCG) dependent on preferred brand of BCG by participating institution. Either 2-8 x 10\^8 CFU for OncoTICE or, 81mg for ImmuCYST and TheraCys. Prior to treatment commencement, investigators should nominate which BCG brand will be used. The same brand of BCG must be used for all treatment administered to an individual participant throughout the study. Dosage of Mitomycin (MM) fixed at 40mg per instillation.
Treatment (Arm A): Intravesical BCG
OTHERInduction (weekly x 6); and followed by Maintenance (monthly x 10) beginning 3 months after randomisation. Dosage of Bacillus of Calmette-Guerin (BCG) dependent on preferred brand of BCG by participating institution. Either 2-8 x 10\^8 CFU for OncoTICE or, 81mg for ImmuCYST and TheraCys. Prior to treatment commencement, investigators should nominate which BCG brand will be used. The same brand of BCG must be used for all treatment administered to an individual participant throughout the study.
Interventions
A strain of tubercle bacillus which modifies biologic response.
An antibiotic produced by a soil actinomycete which inhibits DNA synthesis.
Eligibility Criteria
You may qualify if:
- 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).
- Age \>= 18 yrs
- No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may be either the initial Transurethral Resection of the Bladder Tumour (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.
- ECOG Performance Status of 0-2
- Adequate bone marrow, renal and liver function confirmed by pre-randomisation blood tests.
- Study treatment both planned and able to start within 4 weeks of randomisation
- Has completed the HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision
- Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments
- Signed, written informed consent
You may not qualify if:
- Contraindications or hypersensitivity to investigational products, BCG and Mitomycin
- Prior treatment with any other intravesical agent including BCG or Mitomycin (excludes single doses given post TURBT)
- Current or past transitional cell carcinoma (TCC) of the upper urinary tract
- Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder
- Bladder dysfunction precluding intravesical therapy eg. Severe urinary incontinence or overactive or spastic bladder
- Life expectancy \< 3 months
- Congenital or acquired immune deficiencies, whether due to a concurrent disease (e.g. acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma) or immunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxic drugs, radiation)
- Prior radiotherapy of the pelvis
- Prior or current treatment with radiotherapy-response or biological-response modifiers
- Clinical evidence of existing active tuberculosis
- History of another malignancy within 5 years prior to registration. Patients with non-melanomatous carcinoma of the skin are eligible for this study.
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
- Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Sydneylead
- Australian and New Zealand Urogenital and Prostate Cancer Trials Groupcollaborator
- Cancer Australiacollaborator
Study Sites (17)
Concord Repatriation General Hospital
Concord, New South Wales, 2139, Australia
Nepean Hospital
Kingswood, New South Wales, 2747, Australia
Southside Cancer Care Centre
Miranda, New South Wales, 2228, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, 2305, Australia
GenesisCare
St Leonards, New South Wales, 2065, Australia
The Tweed Hospital
Tweed Heads, New South Wales, 2485, Australia
Sydney Adventist Hospital
Wahroonga, New South Wales, 2076, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Redcliffe Hospital
Redcliffe, Queensland, 4020, Australia
Footscray Hospital
Footscray, Victoria, 3011, Australia
Frankston Hospital
Frankston, Victoria, 3199, Australia
Austin Health - Austin Hospital
Heidelberg, Victoria, 3084, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Royal Melbourne Hospital - City Campus
Parkville, Victoria, 3050, Australia
Epworth Healthcare
Richmond, Victoria, 3121, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Nottingham City Hospital - City Campus
Nottingham, NG7 2UH, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Dickon Hayne
Fiona Stanley Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 1, 2016
First Posted
October 28, 2016
Study Start
July 1, 2013
Primary Completion
December 1, 2024
Study Completion
December 1, 2024
Last Updated
June 18, 2023
Record last verified: 2023-06