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

NCT06462001 | Active Not Recruiting Phase 3

• 1 other identifier: 18UR004
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Transitional Cell Carcinoma; Transurethral Resection

Outcome Measures

Primary Outcomes (1)

• Disease free survival

  Death, disease free survival, or evidence of transitional cell carcinoma (TCC)

  5 years follow up

Secondary Outcomes (10)

• Activity

  3 months

• Time to Recurrence

  5 years follow up

• Time to Progression

  5 years follow up

• Safety and adverse events

  During treatment phase of the trial (typically 12 months)

• Health-Related Quality of Life

  5 years follow up

Other Outcomes (1)

• To consider future exploratory biomarker studies as potential prognostic biomarkers or predictive biomarkers of treatment

  5 years follow up

Study Arms (2)

Arm A: Standard Intravesical BCG

ACTIVE COMPARATOR

Standard intravesical BCG therapy given as per usual standard of care

Biological: Bacillus Calmette-Guerin Vaccine Intravesical

Arm B: Experimental BCG + MM

EXPERIMENTAL

Combination therapy with BCG and MM, given on specific protocol sessions

Biological: Bacillus Calmette-Guerin Vaccine Intravesical; Drug: Mitomycin

Interventions

Bacillus Calmette-Guerin Vaccine Intravesical BIOLOGICAL

BCG (Oncotice) is administered intravesically as per usual standard of care

Arm A: Standard Intravesical BCG; Arm B: Experimental BCG + MM

Mitomycin DRUG

MMC is administered intravesically as per usual standard of care

Arm B: Experimental BCG + MM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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
• Is willing to complete 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

You may not qualify if:

• Contraindications or hypersensitivity to investigational products, BCG and MM
• Prior treatment with any other intravesical agent including BCG or MM (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 e.g. Severe urinary incontinence or overactive or spastic bladder
• Life expectancy \< 3 months
• 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.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: collaborator
• University of Sydney: collaborator

Study Sites (1)

Nottingham University Hospitals

Nottingham, NG51PB, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dickon Hayne, PhD

  The University of Western Australia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: an open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial

Study Record Dates

• First Submitted: December 29, 2023
• First Posted: June 17, 2024
• Study Start: December 10, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 17, 2024

Record last verified: 2024-06

Locations

GB (1)