Study to Evaluate the Non-inferiority of Low-dose HIPEC Versus High-dose HIPEC in the Treatment of PMP (HIPEC-PMP)

HIPEC-PMP is a randomised, non-inferiority phase III trial with two parallel groups, designed to assess two doses of mitomycin C (MMC) for the treatment of pseudomyxoma peritonei. The trial is to be carried out in a single specialist centre.

The low and high doses within the trial are used routinely across the world, but to date they have not been compared directly. As the lead site use low dose MMC, the trial has been designed to assess whether this has comparable performance to high dose with respect to clinical outcomes (primarily disease-free survival; DFS), hence the non-inferiority design. The trial uses a Bayesian design to incorporate existing information on the two treatments (given they are used routinely, and various studies have reported DFS rates in cohort studies). The design allows for discounting the prior information through data-driven weighting of different prior distributions, if the observed data is observed to be markedly different to prior data.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent the standard of care for Pseudomyxoma Peritonei (PMP) of appendiceal origin. Although Mitomycin C is used as standard of care HIPEC treatment, the optimal dose of Mitomycin C (MMC) and duration of HIPEC following cytoreductive surgery remains to be defined.

This study therefore aims to evaluate the non-inferiority of HIPEC with mitomycin C 10 mg/m2 for 60 minutes versus HIEPC with mitomycin C 35 mg/m2 for 90 minutes. There is a small risk of higher toxicity with 35 mg/m2 of Mitomycin C, however Kuijpers et al found that morbidity was tolerable and convincing survival.

There is limited evidence on the quality of life in patients with PMP, therefore assessing quality of life will provide information that could be used to improve patient care and well-being. In addition, furthering understanding of the genetics of the disease could improve prognostication and targeted treatments for patient benefit could be explored and will therefore be investigated in this study. Translational blood samples including tissue (normal, primary and metastatic), serum, plasma, DNA, RNA and buffy coat will be collected for genetic analysis.

Inclusion criteria

• Clinical and/or radiological diagnosis of pseudomyxoma peritonei from a primary mucinous epithelial tumours of the appendix (low and high grade)
• The extent of intraperitoneal disease must be deemed to be amenable to complete cytoreduction (CC0-1, i.e. residual disease of < 2.5mm in diameter).
• Patients aged 16 or more and capable of giving informed consent for the procedures and interventions of the current trial.
• ECOG performance status 0-1.

Exclusion criteria

• Patients who have previously undergone cytoreductive surgery and/or intraperitoneal chemotherapy.
• Clinical evidence or suspicion of metastases to sites different than peritoneum or intra-abdominal lymph nodes
• Hypersensitivity to the active substance (mitomycin) or its excipients (mannitol, hydrochloric acid, sodium hydroxide)
• Patients with conditions which may affect their ability to understand, retain and weigh up the information related to the requirements and consenting process of the study
• Women who are pregnant or breastfeeding.