Adding Mitomycin to BCG as Adjuvant Intravesical Therapy for High-risk Non-Muscle-invasive Bladder Cancer

NCT ID: NCT02948543

Last Updated: 2023-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

501 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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PROTOCOL SYNOPSIS

Background:

Instillation of Bacillus of Calmette-Guerin (BCG) into the urinary bladder (intravesical administration) improves rates of disease recurrence and progression after transurethral resection (TUR) of high risk, non-muscle-invasive bladder cancer (NMIBC), but over 30% of people still develop recurrent transitional cell carcinoma (TCC) despite optimal therapy with adjuvant intravesical BCG. Our meta-analysis, including a recent randomised phase 2 trial, suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both Mitomycin (MM) and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase 3 trial using standard techniques for intravesical administration.

General Aim:

To determine the efficacy and safety of MM in addition to BCG in patients with NMIBC.

Design:

Open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial. Population: The target population is adults with resected, high-risk NMIBC (high grade Ta or any grade T1) suitable for intravesical chemotherapy treatment. Key eligibility criteria include: prior transurethral resection of all visible tumour, adequate organ function, and ECOG performance status 0-2.

Study Treatments:

Arm A: Intravesical BCG Alone (standard): Induction (weekly x 6), followed by Maintenance (monthly x 10); or Arm B: Intravesical BCG + MM (experimental): Induction (weekly x 9), followed by Maintenance (monthly x 9).

Statistical Considerations:

A sample size of 500 (followed until 213 events are observed) provides 85% power to detect a 10% improvement in disease free survival (DFS) rate at 2 years from 70% on BCG alone to 80% on BCG and MM (hazard ratio 0.63) at a significance level of 0.05, allowing for 10% non-compliance.

Conditions

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Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Arm B):Intravesical BCG + MM

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 (MM) fixed at 40mg per instillation.

Group Type EXPERIMENTAL

Bacillus of Calmette-Guerin (BCG)

Intervention Type BIOLOGICAL

A strain of tubercle bacillus which modifies biologic response.

Mitomycin (MM)

Intervention Type DRUG

An antibiotic produced by a soil actinomycete which inhibits DNA synthesis.

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.

Group Type OTHER

Bacillus of Calmette-Guerin (BCG)

Intervention Type BIOLOGICAL

A strain of tubercle bacillus which modifies biologic response.

Interventions

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Bacillus of Calmette-Guerin (BCG)

A strain of tubercle bacillus which modifies biologic response.

Intervention Type BIOLOGICAL

Mitomycin (MM)

An antibiotic produced by a soil actinomycete which inhibits DNA synthesis.

Intervention Type DRUG

Other Intervention Names

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OncoTICE ImmuCYST TheraCys

Eligibility Criteria

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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, renal and liver function confirmed by pre-randomisation blood tests.
6. Study treatment both planned and able to start within 4 weeks of randomisation
7. Has completed the HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision
8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments
9. Signed, written informed consent

Exclusion Criteria

1. Contraindications or hypersensitivity to investigational products, BCG and Mitomycin
2. Prior treatment with any other intravesical agent including BCG or Mitomycin (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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Australian and New Zealand Urogenital and Prostate Cancer Trials Group

OTHER

Sponsor Role collaborator

Cancer Australia

OTHER

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dickon Hayne

Role: STUDY_CHAIR

Fiona Stanley Hospital

Locations

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Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

Nepean Hospital

Kingswood, New South Wales, Australia

Site Status

Southside Cancer Care Centre

Miranda, New South Wales, Australia

Site Status

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Site Status

GenesisCare

St Leonards, New South Wales, Australia

Site Status

The Tweed Hospital

Tweed Heads, New South Wales, Australia

Site Status

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Redcliffe Hospital

Redcliffe, Queensland, Australia

Site Status

Footscray Hospital

Footscray, Victoria, Australia

Site Status

Frankston Hospital

Frankston, Victoria, Australia

Site Status

Austin Health - Austin Hospital

Heidelberg, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital - City Campus

Parkville, Victoria, Australia

Site Status

Epworth Healthcare

Richmond, Victoria, Australia

Site Status

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status

Nottingham City Hospital - City Campus

Nottingham, , United Kingdom

Site Status

Countries

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Australia United Kingdom

Other Identifiers

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12613000513718

Identifier Type: REGISTRY

Identifier Source: secondary_id

ANZUP 1301

Identifier Type: -

Identifier Source: org_study_id

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