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Bladder CancerPhase 3BCG+MMNCT02948543

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

A Phase 3 study testing Bacillus of Calmette-Guerin (BCG) and Mitomycin (MM) in people with Bladder Cancer, run by University of Sydney at 17 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Bacillus of Calmette-Guerin (BCG) and Mitomycin (MM)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
501 participants
Where
17 sitesin 2 countries
Study dates
Jul 2013to Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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.

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

Australia16 sites

  • Concord Repatriation General Hospital

    Concord, New South Wales, 2139

  • Footscray Hospital

    Footscray, Victoria, 3011

  • Frankston Hospital

    Frankston, Victoria, 3199

  • Austin Health - Austin Hospital

    Heidelberg, Victoria, 3084

  • Nepean Hospital

    Kingswood, New South Wales, 2747

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Southside Cancer Care Centre

    Miranda, New South Wales, 2228

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

  • Royal Melbourne Hospital - City Campus

    Parkville, Victoria, 3050

  • Redcliffe Hospital

    Redcliffe, Queensland, 4020

  • Epworth Healthcare

    Richmond, Victoria, 3121

  • GenesisCare

    St Leonards, New South Wales, 2065

  • The Tweed Hospital

    Tweed Heads, New South Wales, 2485

  • Sydney Adventist Hospital

    Wahroonga, New South Wales, 2076

  • Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

United Kingdom1 site

  • Nottingham City Hospital - City Campus

    Nottingham, NG7 2UH

Other trials in United Kingdom

About this study

Official title: 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

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.

Read the detailed description

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
Bladder Cancer
Being tested
Bacillus of Calmette-Guerin (BCG), Mitomycin (MM)
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bacillus of Calmette-Guerin (BCG)Biological

    Also called OncoTICE, ImmuCYST, TheraCys

    A strain of tubercle bacillus which modifies biologic response.

  • Mitomycin (MM)Drug

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

Study groups in NCT02948543
Study groupRoleWhat they receive
Treatment (Arm B):Intravesical BCG + MMExperimentalInduction (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.
Receives: Biological: Bacillus of Calmette-Guerin (BCG); Drug: Mitomycin (MM)
Treatment (Arm A): Intravesical BCGOtherInduction (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.
Receives: Biological: Bacillus of Calmette-Guerin (BCG)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 5 years

Secondary outcomes (8)

  1. Activity (Clear cystoscopy at 3 months)

    Treatment activity is defined as a negative cystoscopy \& biopsy at nominal week 12 (i.e. after induction therapy, but prior to the commencement of maintenance therapy). Assessed via cystoscopy and biopsy.

    Measured: At 3 months after patient randomised

  2. Time to recurrence (recurrence)

    Measured from the date of randomisation until the first date recurrence is detected. Disease recurrence is defined as evidence on cystoscopy or biopsy of Ta or T1-4 disease, or if there is evidence of metastatic disease. Assessed via cystoscopy.

    Measured: Up to 5 years

  3. Time to progression (disease progression)

    Measured from the date of randomisation until the first date progression is detected. Disease progression is defined as evidence of disease that is of a higher grade or a higher stage than at baseline. Assessed via cystoscopy.

    Measured: Up to 5 years

  4. Safety (Adverse events graded according to CTC AE V4.0)

    The NCI Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events after each treatment cycle.

    Measured: Measured before day 1 of each instillation during treatment.

  5. 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).

    Measured: Up to 5 years from the date of randomisation

  6. Overall survival time (death from any cause)

    Overall survival is defined as the interval from the date of randomisation to the date of death from any cause or the date last known to be alive.

    Measured: Up to 5 years

  7. Treatment Completion

    Treatment completion is defined as having received 75% or more of the planned numbers of induction and maintenance doses.

    Measured: Measured at end of study treatment (12 months after patient randomized).

  8. Marginal resource use

    Assessed via a specifically designed resource utilisation form (collecting information such as number, type and duration of visits).

    Measured: 5 years after last patient randomized (or date last patient has died, whichever sooner).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2016 (estimated)
  2. Study startJul 2013
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
501 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02948543
Sponsor's protocol ID
ANZUP 1301
Other IDs
12613000513718
Acronym
BCG+MM
Status last verified
Jun 2023
First submitted
1 Aug 2016
Last updated
18 Jun 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bacillus of Calmette-Guerin (BCG) and Mitomycin (MM) in people with Bladder Cancer, run by University of Sydney at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease free survival (death or recurrence) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02948543.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.

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BCG+MM Clinical Trial NCT02948543 | AzTrials