HIVEC® HEAT (Hyperthermic intravesical mitomycin mEdac) for pAtients with BCG-unresponsive nonmuscle-invasive bladder cancer Trial
Non-Muscle-Invasive Bladder Cancer (NMIBC)
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 in 40 mL of saline. Another 40 mL of saline is added to prime the BRS tubing set totalling 80 mL saline overall. Therefore, the concentration of Mitomycin medac that will be recirculated into the bladder will be 1 mg/mL. Participants will receive 80 mg Mitomycin medac at a dose of 1 mg/mL for 12 months of treatment. The total number of HIVEC® treatments over 12 months is fifteen. Participants will be followed up for 24 months in total, including during 12 months of treatment recirculation and every 3 months thereafter for another 12 months (month 15, month 18, month 21, and month 24). The follow-up visits will follow the same schedule as standard of care. If a patient discontinues treatment early, every effort should be made to ensure treatment related AEs are recorded either by an in-person clinic visit or via the telephone at 12 months
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 T
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.