New Hope for Patients with BCG-Unresponsive NMIBC
Combat Medical is proud to announce the commencement of the HIVEC®-HEAT phase 3 trial – the main aim being to evaluate the effectiveness of our hyperthermic intravesical chemotherapy (HIVEC®) treatment with 80mg mitomycin medac as an alternative to radical cystectomy (RC). Interim data from the study are expected in 2026 and will provide early insights into the treatment’s performance. Now that this trial has officially received ethical and MHRA approval, we can take the next step towards offering patients an effective, bladder-sparing alternative to RC, which has long been the standard of care for high-risk cases that do not respond to BCG therapy.
About the HIVEC®-HEAT Trial
The HIVEC®-HEAT study is a multi-centre, single-arm, interventional phase 3 clinical trial sponsored by the University of Leicester. The study is led by Professor Leyshon Griffiths, Associate Professor and Honorary Consultant Urological Surgeon at the University of Leicester and University Hospitals of Leicester NHS Trust. This clinically initiated trial is funded by Combat Medical and supported by the NIHR.
Set to enrol 238 patients across up to 25 NHS hospitals in the UK, this trial is a major collaborative effort involving urology experts, researchers, and NHS clinical sites. The first patient is expected to enrol by May 2025.
Structure and Objectives of the Trial
Recruitment is taking place at up to 25 NHS hospitals in the UK, with the first patient expected to enrol by May 2025. With 238 patients in total, the trial includes two separate studies:
- Sub-Study 1 – 123 patients with BCG-unresponsive carcinoma in situ (CIS), with or without completely resected papillary Ta/T1 disease. The primary outcome measure is complete response (CR) at three months.
- Sub-Study 2 – 115 patients with completely resected BCG-unresponsive, high-grade papillary Ta/T1 disease, without CIS. The primary outcome measure is high-grade, recurrence-free survival time.
An Urgent Need for Alternatives to Radical Cystectomy
For decades, radical cystectomy has been the standard of care for patients with BCG-unresponsive high-risk NMIBC. While this procedure offers a curative outcome in 80–90% of cases when performed before progression to muscle-invasive bladder cancer, it comes at a significant physical and emotional cost. Radical cystectomy is a major surgery associated with considerable morbidity, postoperative complications, and even mortality, particularly in older patients or those with comorbidities.
Furthermore, some patients opt against RC due to concerns about the profound impact on their quality of life, including the need for urinary diversion and changes in bodily function.
What Is HIVEC® and How Does It Work?
HIVEC® (Hyperthermic Intravesical Chemotherapy) is a novel, non-surgical treatment that delivers warmed chemotherapy directly into the bladder via a controlled recirculation system. The heat enhances the drug’s effectiveness, improving penetration into the bladder wall and boosting its cytotoxic activity. By using mitomycin C, a well-established chemotherapy agent, in a heated state, HIVEC® amplifies the therapeutic effects while maintaining a strong safety profile.
Numerous retrospective and prospective studies [1][2] have demonstrated the safety and clinical effectiveness of HIVEC® in treating patients with high-risk NMIBC who are unresponsive to BCG. The treatment has been well tolerated by patients and offers the crucial advantage of bladder preservation, helping to maintain quality of life without compromising cancer control.
Endorsement and Progress Towards FDA Recognition
Edward Bruce-White, CEO of Combat Medical, commented on the approval, saying:
“The HIVEC®-HEAT trial has been positively reviewed by the FDA, and the first sites have completed site-initiation visits. We are therefore delighted to have reached this next important milestone and have the green light for patient recruitment. Prospective and retrospective studies have demonstrated HIVEC®’s efficacy and use as a safe and well-tolerated, bladder-sparing alternative to radical cystectomy in BCG-unresponsive, high-risk NMIBC. It has also been shown to be a highly cost-effective therapeutic option, with greater efficacy and at a far lower cost than pembrolizumab.”
A Cost-Effective, Life-Changing Option
HIVEC® is also a cost-effective treatment option compared with pembrolizumab, for example, as highlighted in the recent guidelines published in BJUI [3]. This report showed that HIVEC® provides a more affordable route to disease control without compromising safety or patient outcomes, making it an appealing option for both patients and healthcare systems facing rising treatment costs.
The Way Forward
If successful, our trial will hopefully pave the way for a new standard of treatment for BCG-unresponsive NMIBC, for not only treating bladder cancer effectively, but also preserving the dignity, quality of life, and hope of cancer patients worldwide.
For further updates please contact Guy Cooper
[1] Pijpers OM et al. J Urol Oncol, 2022.
[2] Stemberger A et al. J Urol, 2022.
[3] Rieger C et al. BJUI, 2024. [4] EAU guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). Eur Urol, 2022 [5] Stein JP et al. J Clin Oncol, 2001
