Clinical trial NCT06462001: BCG + MMC: Adding Mitomycin C to BCG in High-risk, Non-muscle-invasive Bladder Cancer
Official title: BCG + MMC: Adding Mitomycin C to BCG as Adjuvant Intravesical Therapy for High-risk, Non-muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Transitional Cell Carcinoma
Transurethral Resection
Lead sponsor: Nottingham University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
name: University of Sydney
First posted: 2024-06-17
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: an open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial
Primary purpose: TREATMENT

Brief 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.


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.

Primary outcomes:
measure: Disease free survival
timeFrame: 5 years follow up
Secondary outcomes:
measure: Activity
timeFrame: 3 months
measure: Time to Recurrence
timeFrame: 5 years follow up
measure: Time to Progression
timeFrame: 5 years follow up
measure: Safety and adverse events
timeFrame: During treatment phase of the trial (typically 12 months)
measure: Health-Related Quality of Life
timeFrame: 5 years follow up
measure: Health-Related Quality of Life
timeFrame: 5 years follow up
measure: Health-Related Quality of Life
timeFrame: 5 years follow up
measure: Overall Survival Time
timeFrame: 5 years follow up
measure: Feasibility as a future standard of care
timeFrame: During treatment phase of the trial, typically 1 year
measure: Marginal Resource Use
timeFrame: 5 years follow up
Other outcomes:
measure: To consider future exploratory biomarker studies as potential prognostic biomarkers or predictive biomarkers of treatment
timeFrame: 5 years follow up
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
affiliation: The University of Western Australia
name: Dickon Hayne, PhD
role: STUDY_DIRECTOR
References: