Non-Muscle-Invasive Bladder Cancer (NMIBC) Cancer
Conditions
Interventions
Hyperthermic Intravesical Chemotherapy (HIVEC®) in this study is conducted with the Combat BRS system (COMBRS05) and combined with Mitomycin medac administered at a concentration dose of 80 mg diluted
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Under white light cystoscopy, diagnosis of urothelial carcinoma of the bladder with histologic confirmation of a tumour containing at least one (more than one allowed) of the following stage and grade categories: 1.1. Ta, high-grade 1.2. T1, high-grade 1.3. Carcinoma in situ (CIS) 2. Must be BCG-unresponsive as defined by any of the following situations: 2.1. Refractory disease (no response to BCG) 2.1.1. High-grade papillary T1 disease at 3 months following induction BCG treatment. 2.1.2. High-grade papillary Ta/T1 disease and/or CIS at 6 months after completion of adequate BCG exposure 2.1.3. (Adequate BCG is defined as at least 5 out of 6 doses of an initial induction course, plus at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction) 2.2. Relapsing disease (relapse after initial response to BCG) 2.2.1. Within 6 months of last dose of adequate BCG exposure (defined above), the presence of recurrent high-grade papillary Ta/T1 disease is detected 2.2.2. Within 12 months of last dose of adequate BCG exposure (defined above), the presence of recurrent CIS is detected 3. Complete transurethral resection of all Ta/T1 tumour under white light within 6 weeks of first HIVEC® treatment. A complete transurethral resection consists of the removal of all visible papillary (Ta/T1) tumour. 4. Repeat white light cystoscopy is required prior to initiating HIVEC® if the time interval from the most recent TURBT to HIVEC® is > 6 weeks. This is to ensure there is no recurrent visible papillary/solid tumour. 5. Repeat (second-look) TURBT under white light is required prior to initiating HIVEC® in the following instances: 5.1. Absence of detrusor muscle in pathology specimen for high-grade Ta/T1 tumours. [If after the repeat (second-look) TURBT there is still absence of detrusor muscle in the pathology specimen for high-grade Ta, then there must be no visible papillary tumour (and confirmed as benign or remains high-grade Ta)] 5.2. High-grade T1 tumours whether detrusor muscle is present or not 6. Able and willing to provide signed and written informed consent 7. Unsuitable for cystectomy or who are unwilling to undergo cystecomy preferring a bladder-sparing approach. 8. Age =18 years 9. WHO performance status =2 10. Negative serum pregnancy test for women of child-bearing potential within 14 days of treatment initiation. 11. Women of child-bearing potential and/ or male participants must agree to use highly effective methods of birth control
Exclusion criteria
Exclusion criteria: 1. BCG-unresponsive urothelial carcinoma that has been detected with enhanced cystoscopic techniques. 2. A history of muscle-invasive (T2, T3, T4), lymph node-positive (N1, N2, N3), or metastatic (M1) bladder cancer. 3. High-grade T1 NMIBC where lymphovascular invasion is reported. 4. Histology subtypes of bladder cancer other than pure urothelial carcinoma, excluding urothelial carcinoma with squamous or glandular differentiation which are permissible. 5. Unlikely to complete or adhere to the clinical trial due to: 5.1. Life expectancy <2 years. 5.2. Unable or unwilling to receive the required follow-up care or diagnostic interventions. 6. Any condition that, in the opinion of the investigator, could lead to protocol non-compliance. 7. Any pelvic radiotherapy. 8. Prior salvage immunotherapy or chemotherapy for BCG-U NMIBC. 9. Participants must not have received any live or live attenuated vaccine within 4 weeks of the first treatment. 10. Unresolved bladder perforation 11. History of urothelial carcinoma of the upper urinary tract (ureter, renal pelvis) or prostatic urethra within 24 months of treatment initiation. 12. Mitomycin-C allergy. 13. Inability to undergo HIVEC® treatment: 13.1. Urinary frequency or urgency that precludes a 1-hour HIVEC® dwell time. 13.2. Urethral stricture preventing urethral catheterisation with the Combat BRS system 16 F catheter. 14. Uncontrolled visible haematuria. 15. Active or untreated urinary tract infection. 16. Pregnancy, breastfeeding, or planning to conceive during the treatment and/or the post-treatment period. 17. Participant must not be simultaneously enrolled in any interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sub-Study 1. Complete response (CR) at 3 months (negative cystoscopy without evidence of recurrent CIS in the bladder and a urine cytology test 'not positive' for high-grade urothelial carcinoma) Sub-Study 2. Median duration of high-grade recurrence-free survival (whole days from first HIVEC treatment to first evidence of high-grade recurrence or death) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoints are as and when the outcome occurs. Each follow-up is essential in the treatment pathway to ensure patients remain free from recurrence and/or progression. No one result/CRF will provide a definitive diagnosis and the evidence is collated across all these follow-ups to ensure these outcomes are met. 1. Freedom from high-grade Ta/T1 or CIS 2. Freedom from non-bladder recurrence of urothelial cancer 3. Progression-free survival 4. Cystectomy-free survival 5. Disease-specific survival 6. Overall survival from follow ups In addition to those secondary outcomes listed above, those in Sub-study 1 will also look at: 1. Median duration of CR (from date of CR to first evidence of high-grade recurrence or date of last follow-up if no recurrence develops) 2. Complete response (CR) rate at 6, 12 and 24 months (negative cystoscopy without evidence of recurrent CIS in the bladder and a urine cytology test 'not positive' for high-grade urothelial carcinoma) | — |
Countries
England, United Kingdom
Outcome results
None listed