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.

In patients with high-risk, non–muscle-invasive bladder cancer, is adding mitomycin to BCG for adjuvant intravesical therapy as good as or better than BCG alone for disease free survival?

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12613000513718

Acronym

BCG+MM

Enrollment

501

Registered

2013-05-08

Start date

2013-12-16

Completion date

2023-05-17

Last updated

2025-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Summary The purpose of this study is to determine the effect of adding mitomycin (a chemotherapy drug) to best current treatment in patients with high-risk non-muscle invasive bladder cancer. Who is it for? You may be eligible to join this study if you are at least 18 years of age and have been diagnosed with non-muscle invasive bladder cancer. You should have undergone transurethral resection of the bladder tumour (TURBT) within 8 weeks prior to enrolment with no visible disease remaining. Trial details Non-muscle invasive bladder cancer is common, causes substantial suffering, and requires radical removal or irradiation of the bladder within 5 years in over 30% of people with high risk tumours despite best current treatment. Recent preliminary studies show promising results from adding mitomycin, a chemotherapy drug, to best current treatment with BCG. Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will receive the current standard treatment. This involves direct instillation of the drug, Bacillus of Calmette-Guerin (BCG) into the bladder weekly for 6 weeks, and then monthly for 10 months. Participants in the other group with receive BCG and the chemotherapy drug, mitomycin, via instillation into the bladder weekly for 9 weeks, and then monthly for 9 months. Participants will be regularly assessed for up to 5 years in order to determine the effects of adding mitomycin on cure rates, survival, side effects, and quality of life.

Interventions

Experimental Treatment (Arm B): Intravesical Bacillus of Calmette-Guerin (BCG) + Mitomycin (MM). Induction (weekly x 9); and followed by Maintenance (monthly x 9) beginning 3 months after randomisation. Standard dosing: BCG OncoTICE 2-8 x 10^8 CFU Mitomycin 40mg per instillation

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

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 greater than or equal to 18 yrs 3. No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may either be the initial 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. Is willing to complete 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 MM 2. Prior treatment with any other intravesical agent including BCG or MM (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 e.g. 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.

Outcome results