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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02948543




Registration number
NCT02948543
Ethics application status
Date submitted
1/08/2016
Date registered
28/10/2016
Date last updated
9/05/2018

Titles & IDs
Public title
Adding Mitomycin C to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer
Scientific title
Adding Mitomycin C to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial
Secondary ID [1] 0 0
12613000513718
Secondary ID [2] 0 0
ANZUP 1301
Universal Trial Number (UTN)
Trial acronym
BCG+MMC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Bacillus of Calmette-Guerin (BCG)
Treatment: Drugs - Mitomycin C (MMC)

Experimental: Treatment (Arm B):Intravesical BCG + MMC - Induction (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 (MMC) fixed at 40mg per instillation.

Other: Treatment (Arm A): Intravesical BCG - Induction (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.


Other interventions: Bacillus of Calmette-Guerin (BCG)
A strain of tubercle bacillus which modifies biologic response.

Treatment: Drugs: Mitomycin C (MMC)
An antibiotic produced by a soil actinomycete which inhibits DNA synthesis.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease free survival (death or recurrence)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Activity (Clear cystoscopy at 3 months)
Timepoint [1] 0 0
At 3 months after patient randomised
Secondary outcome [2] 0 0
Time to recurrence (recurrence)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Time to progression (disease progression)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Safety (Adverse events graded according to CTC AE V4.0)
Timepoint [4] 0 0
Measured before day 1 of each instillation during treatment.
Secondary outcome [5] 0 0
Health-Related Quality of Life - Health related quality life is a composite outcome aggregated to arrive at one reported value to ensure multiple aspects of the participants life are adequately assessed and measured. The following questionnaires will be used; the 24-item EORTC Bladder Symptoms Quality of Life module (QLM-BLS24); the EORTC Core Quality of Life Questionnaire (QLQ-C30); and the International Prostate Symptom Score (I-PSS).
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Overall survival time (death from any cause)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Treatment Completion - Treatment completion is defined as having received 75% or more of the planned numbers of induction and maintenance doses.
Timepoint [7] 0 0
Measured at end of study treatment (12 months after patient randomized).
Secondary outcome [8] 0 0
Marginal resource use - Assessed via a specifically designed resource utilisation form (collecting information such as number, type and duration of visits).
Timepoint [8] 0 0
5 years after last patient randomized (or date last patient has died, whichever sooner).

Eligibility
Key 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 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.

4. ECOG Performance Status of 0-2

5. Adequate bone marrow function

6. Adequate renal function

7. Adequate liver function

8. Study treatment both planned and able to start within 4 weeks of randomisation

9. Has completed the HRQL questionnaires or is unable to complete them because of
literacy, insufficient English or limited vision

10. Willing and able to comply with all study requirements, including treatment, timing
and/or nature of all required assessments

11. Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindications or hypersensitivity to investigational products, BCG and Mitomycin C

2. Prior treatment with any other intravesical agent including BCG or Mitomycin C
(excludes single doses given post TURBT)

3. Current or past transitional cell carcinoma (TCC) of the upper urinary tract

4. Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder

5. Bladder dysfunction precluding intravesical therapy eg. Severe urinary incontinence or
overactive or spastic bladder

6. Life expectancy < 3 months

7. 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)

8. Prior radiotherapy of the pelvis

9. Prior or current treatment with radiotherapy-response or biological-response modifiers

10. Clinical evidence of existing active tuberculosis

11. History of another malignancy within 5 years prior to registration. Patients with
non-melanomatous carcinoma of the skin are eligible for this study.

12. Serious medical or psychiatric conditions that might limit the ability of the patient
to comply with the protocol.

13. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Northern Cancer Institute, St Leonards - St Leonards
Recruitment hospital [3] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [4] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [5] 0 0
Footscray Hospital - Footscray
Recruitment hospital [6] 0 0
Frankston Hospital - Frankston
Recruitment hospital [7] 0 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [9] 0 0
Royal Melbourne Hospital - City Campus - Parkville
Recruitment hospital [10] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [4] 0 0
2076 - Wahroonga
Recruitment postcode(s) [5] 0 0
3011 - Footscray
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3050 - Parkville
Recruitment postcode(s) [10] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cancer Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Open label, randomised phase 3 trial of the addition of Mitomycin C 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 Mitomyicn C in
addition to BCG.
Trial website
https://clinicaltrials.gov/show/NCT02948543
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dickon Hayne
Address 0 0
Fiona Stanley Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BCG+MMC Trial Coordinator
Address 0 0
Country 0 0
Phone 0 0
+61 2 9562 5000
Fax 0 0
Email 0 0
bcgmmc@ctc.usyd.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02948543