May 23 2024 – Combat Medical has entered into partnership with the University of Leicester, England, to run a phase 3 trial of its HIVEC® treatment for BCG-unresponsive nonmuscle-invasive bladder cancer (NMIBC) as an alternative to radical cystectomy.
HIVEC®-HEAT – HIVEC® (Hyperthermic intravesical mitomycin mEdac) for pAtients with BCG-unresponsive nonmuscle-invasive bladder cancer Trial – will be a multi-centre, single-arm interventional trial across 25 NHS hospitals in the United Kingdom (UK). Currently awaiting MRHA approval, and already reviewed by the FDA, it is expected to start recruiting the first of 238 patients in September, with a two-year recruitment period and two-year follow-up.
Funded by Combat Medical, adopted by the National Institute for Health and Care Research and sponsored by the University of Leicester, the investigator-initiated study will be led by Professor Leyshon Griffiths, Associate Professor/Honorary Consultant Urological Surgeon at the University of Leicester & University Hospitals of Leicester NHS Trust.
Professor Griffiths said: “Why should eligible patients in the UK consider joining the HIVEC®-HEAT trial? Firstly, HIVEC® treatments will recirculate heated mitomycin medac in participants’ bladders at double the concentration (1 mg/mL) compared with standard HIVEC® practice (0.5 mg/mL). Secondly, participants will receive up to 15 HIVEC® treatments over one year – many patients receive less out of trial in UK centres.”
Combat Medical CEO Edward Bruce-White commented: “HIVEC®’s use as a safe and well-tolerated bladder-sparing alternative to radical cystectomy in BCG-unresponsive, high-risk NMIBC has already been demonstrated in a series of smaller prospective and retrospective studies.[1,2] A recent analysis has also shown it to be a highly cost-effective therapeutic option, with greater efficacy and at a far lower cost than the FDA-approved pembrolizumab. With 100,000+ treatments already completed in more than 40 countries, we are confident this phase 3 trial will prove that HIVEC® will be a game-changer in the treatment of high-risk, BCG-unresponsive patients, especially at a time of acute BCG shortages worldwide.”
Some 573,000 patients are diagnosed with bladder cancer every year,[3] and around 70-85% present with NMIBC.[4] Current treatment comprises complete resection of visible tumour, with adjuvant BCG intravesical installation recommended to reduce the risk of recurrence and progression in patients with high-risk NMIBC.[5] However, tumours recur in at least 40-50% of these patients, with 10-20% progressing to muscle-invasive or metastatic bladder cancer.[6]
The standard of care for BCG-unresponsive patients is radical cystectomy,[3] involving removal of the bladder together with nearby lymph nodes, and often part of the bowel, the prostate gland and seminal vesicles in males, and the womb and fallopian tubes in females. It is curative in 80-90% if performed prior to progression to muscle-invasive bladder cancer.[7] However, radical cystectomy may not be a suitable treatment alternative as it is associated with a higher degree of morbidity and mortality, while some patients refuse it on quality-of-life grounds.
- Pijpers OM et al., Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle-invasive bladder cancer. Journal of Urologic Oncology, 2022. Feb; 40(2):62.e13-62.e20. Epub 2021 Aug 30. https://doi.org/10.1016/j.urolonc.2021.07.0197
- Stemberger A et al., MP54-15: A multicenter study of 2-year outcomes following hyperthermia therapy with mitomycin C in treating BCG-unresponsive non-muscle-invasive bladder cancer: recirculant hyperthermic intravesical chemotherapy. The Journal of Urology, 2022. May 1. doi.org/10.1097/JU.0000000000002633.15
- Zhang Y et al., The global landscape of bladder cancer incidence and mortality in 2020 and projections to 20240. Journal of Global Health, 2023. 13. https://jogh.org/2023/jogh-13-04109
- Griffiths TL and Action on Bladder Cancer, Current perspectives in bladder cancer management. International Journal of Clinical Practice, 2013. 67(5):435-488. https://onlinelibrary.wiley.com/doi/10.1111/ijcp.12075
- EAU guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). European Urology 2022; available from https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-Guidelines-on-Non-Muscle-Invasive-Bladder-Cancer-2022.pdf
- Witjes JA. Management of BCG failures in superficial bladder cancer: a review. European Urology, 2006. 49(5):790-797. https://www.sciencedirect.com/science/article/abs/pii/S0302283806000352?via%3Dihub
- Stein JP et al., Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. Journal of Clinical Oncology, 2001. 19(3):666-675. https://doi.org/10.1200/JCO.2001.19.3.6
