Transitional Cell Carcinoma, Transurethral Resection
Conditions
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.
Interventions
BIOLOGICALBacillus Calmette-Guerin Vaccine Intravesical
BCG (Oncotice) is administered intravesically as per usual standard of care
DRUGMitomycin
MMC is administered intravesically as per usual standard of care
Sponsors
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
University of Sydney
Nottingham University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
an open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival | 5 years follow up | Death, disease free survival, or evidence of transitional cell carcinoma (TCC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activity | 3 months | Clear cystoscopy at 3 months |
| Time to Recurrence | 5 years follow up | Recurrence of TCC bladder |
| Time to Progression | 5 years follow up | Recurrence of Higher Grade or Stage |
| Safety and adverse events | During treatment phase of the trial (typically 12 months) | Adverse Events Graded According to CTC AE V4.03 |
| Overall Survival Time | 5 years follow up | Death from any Cause |
| Feasibility as a future standard of care | During treatment phase of the trial, typically 1 year | Compliance with intravesical therapy, measured in percent (%) of planned intravesical therapies actually given |
| Marginal Resource Use | 5 years follow up | Number of GP visits, Number of outpatient and emergency department visits, number of inpatient admissions and number of days admitted |
| Health-Related Quality of Life | 5 years follow up | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To consider future exploratory biomarker studies as potential prognostic biomarkers or predictive biomarkers of treatment | 5 years follow up | Future (as yet unidentified) biomarker expression could be measured and then statistical association of those biomarkers with primary outcome meaures assessed. |
Countries
United Kingdom
Outcome results
None listed