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

Transitional Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06462001
• Other study ID #: 18UR004
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 10, 2020
• Est. completion date: December 1, 2026

Study information

• Verified date: June 2024
• Source: Nottingham University Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 1, 2026
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Transitional Cell Carcinoma
• Transurethral Resection

Intervention

Biological:
• Bacillus Calmette-Guerin Vaccine Intravesical
BCG (Oncotice) is administered intravesically as per usual standard of care

Drug:
• Mitomycin
MMC is administered intravesically as per usual standard of care

Locations

Country	Name	City	State
United Kingdom	Nottingham University Hospitals	Nottingham

Sponsors (3)

Lead Sponsor	Collaborator
Nottingham University Hospitals NHS Trust	Australian and New Zealand Urogenital and Prostate Cancer Trials Group, University of Sydney

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To consider future exploratory biomarker studies as potential prognostic biomarkers or predictive biomarkers of treatment	Future (as yet unidentified) biomarker expression could be measured and then statistical association of those biomarkers with primary outcome meaures assessed.	5 years follow up
Primary	Disease free survival	Death, disease free survival, or evidence of transitional cell carcinoma (TCC)	5 years follow up
Secondary	Activity	Clear cystoscopy at 3 months	3 months
Secondary	Time to Recurrence	Recurrence of TCC bladder	5 years follow up
Secondary	Time to Progression	Recurrence of Higher Grade or Stage	5 years follow up
Secondary	Safety and adverse events	Adverse Events Graded According to CTC AE V4.03	During treatment phase of the trial (typically 12 months)
Secondary	Health-Related Quality of Life	QLQ-BLS24. Individual internationally-validated (but subjective) symptom score questionnaire that gives an overall QOL assesment, that can be tracked throughout follow up. They do not use SI units of measurement.	5 years follow up
Secondary	Health-Related Quality of Life	QLQ-C30. Individual internationally-validated (but subjective) symptom score questionnaire that gives an overall QOL assesment, that can be tracked throughout follow up. They do not use SI units of measurement.	5 years follow up
Secondary	Health-Related Quality of Life	I-PSS. Individual internationally-validated (but subjective) symptom score questionnaire that gives an overall QOL assesment, that can be tracked throughout follow up. They do not use SI units of measurement.	5 years follow up
Secondary	Overall Survival Time	Death from any Cause	5 years follow up
Secondary	Feasibility as a future standard of care	Compliance with intravesical therapy, measured in percent (%) of planned intravesical therapies actually given	During treatment phase of the trial, typically 1 year
Secondary	Marginal Resource Use	Number of GP visits, Number of outpatient and emergency department visits, number of inpatient admissions and number of days admitted	5 years follow up