BCG + MMC: Adding Mitomycin C to BCG in High-risk, Non-muscle-invasive Bladder Cancer

Trial Title: BCG + MMC: Adding Mitomycin C to BCG in High-risk, Non-muscle-invasive Bladder Cancer

NCT ID: NCT06462001

Condition: Transitional Cell Carcinoma
Transurethral Resection

Conditions: Official terms:
Non-Muscle Invasive Bladder Neoplasms
Carcinoma, Transitional Cell
Mitomycins
Mitomycin
BCG Vaccine

Study type: Interventional

Study phase: Phase 3

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: an open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Bacillus Calmette-Guerin Vaccine Intravesical
Description: BCG (Oncotice) is administered intravesically as per usual standard of care
Arm group label: Arm A: Standard Intravesical BCG
Arm group label: Arm B: Experimental BCG + MM

Intervention type: Drug
Intervention name: Mitomycin
Description: MMC is administered intravesically as per usual standard of care
Arm group label: Arm B: Experimental BCG + MM

Summary: 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.

Criteria for eligibility:
Criteria:
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 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Nottingham University Hospitals

Address:
City: Nottingham
Zip: NG51PB
Country: United Kingdom

Start date: December 10, 2020

Completion date: December 1, 2026

Lead sponsor:
Agency: Nottingham University Hospitals NHS Trust
Agency class: Other

Collaborator:
Agency: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Agency class: Other

Collaborator:
Agency: University of Sydney
Agency class: Other

Source: Nottingham University Hospitals NHS Trust

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06462001