Evaluating the non-inferiority of HIPEC with mitomycin C 10 mg/m2 for 60 min versus HIPEC with mitomycin C 35 mg/m2 for 90 min in the treatment of pseudomyxoma peritonei from perforated epithelial mucinous tumours of the appendix (HIPEC-PMP): protocol for a single-blinded, randomised controlled trial
5 affiliations
- 1Cancer Research UK Southampton Clinical Trials Unit, University of Southampton, Southampton, Hampshire, UK
- 2University Hospital Southampton NHS Foundation Trust, Southampton, UK
- 3Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Winchester, UK
- 4MRC Biostatistics Unit, University of Cambridge, Cambridge, UK
- 5Southampton Health Technologies Assessment Centre, University of Southampton, Southampton, UK
Abstract
Introduction: Pseudomyxoma peritonei (PMP) is a rare malignancy usually originating from a perforated appendix tumour. Potentially curative treatment involves cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy, commonly mitomycin-C (MMC). Different regimens of MMC are used across the world, with little convincing evidence for which regimen best balances favourable clinical outcomes against side effects and cost. The aim of this trial is to compare two dosing regimens of MMC during CRS.
Methods and analysis: The HIPEC-PMP trial is an individually randomised, parallel group, single-blind, non-inferiority trial that will randomise patients (1:1) with PMP who are amenable to complete cytoreduction to one of two established regimens, either low-dose MMC (10 mg/m2 for 60 min) or high-dose MMC (35 mg/m2 for 90 min) to test the non-inferiority of low-dose MMC. A Bayesian design is used to incorporate prior information on each dose, with a principled approach to discount historical data if it is markedly different from the trial data. Participants must have a clinical and/or radiological diagnosis of PMP from a primary mucinous epithelial tumour of the appendix that is amenable to complete cytoreduction and will be recruited from a single specialist centre. Participants will be followed up for a minimum of 2 years. The primary endpoint is disease-free survival at 2 years, and secondary endpoints are overall survival, adverse events, quality of life and cost-effectiveness. A Bayesian analysis will be used to determine the probability that 2-year recurrence rates are within 10% to determine non-inferiority. The trial has a target sample size of 176.
Ethics and dissemination: The study is sponsored by the University of Southampton, coordinated by the Cancer Research UK Southampton Clinical Trials Unit, and open to recruitment at the Peritoneal Malignancy Unit at the Hampshire Hospitals Foundation Trust. The trial protocol has received the favourable opinion of the London-Westminster Research Ethics Committee (REC 24/LO/0692), as well as the necessary approvals from the Medicines and Healthcare products Regulatory Agency and NHS Health Research Authority. Informed consent is required before any trial specific procedures are undertaken. It is intended that the results of the study will be disseminated via publication in peer-reviewed scientific journals, conference presentations and submission to regulatory authorities.
Trial registration number: NCT06513065.
Related
- Immunogenicity and safety of Sabin inactivated poliovirus vaccine in a sequential schedule with bivalent oral poliovirus vaccine in Nepal: a single-centre, double-blind, randomised, controlled, non-inferiority trial
- Lifestyle therapy versus cognitive behavioural therapy for adults with mood disorders: a randomised non-inferiority trial
- Evaluation of percutaneous cryoneurotomy compared with surgical open neurotomy for the management of post-stroke spastic equinovarus foot in France: protocol for a multicentre, randomised controlled, open-label, non-inferiority trial
- A randomised non-inferiority trial of CCTA guidance versus IVUS guidance for PCI: rationale and design of the P4 clinical trial
- Lesion sterilisation and tissue repair with chloramphenicol, tetracycline, zinc oxide-eugenol paste compared to zinc oxide-eugenol pulpectomy in primary molars: Two-year follow-up findings of a multicentre non-inferiority randomised clinical trial
BibTeX
@article{ewings2026evaluating,
title = {{Evaluating the non-inferiority of HIPEC with mitomycin C 10 mg/m2 for 60 min versus HIPEC with mitomycin C 35 mg/m2 for 90 min in the treatment of pseudomyxoma peritonei from perforated epithelial mucinous tumours of the appendix (HIPEC-PMP): protocol for a single-blinded, randomised controlled trial}},
author = {Sean Ewings and Sophia Stanford and Chris Wignall and Karen Martin and Pavel Mozgunov and Gianmarco Caruso and Louise Holmes and Paul Smith and David Scott and Gareth Griffiths and Alexios Tzivanakis and Sanjeev Dayal and Vasanth Mark Samuel and Gui Han Lee and Brendan Moran and Faheez Mohamed and Tom Cecil},
journal = {BMJ Open Gastroenterology},
year = {2026},
month = nov,
doi = {10.1136/bmjgast-2025-002187},
url = {https://doi.org/10.1136/bmjgast-2025-002187},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Evaluating the non-inferiority of HIPEC with mitomycin C 10 mg/m2 for 60 min versus HIPEC with mitomycin C 35 mg/m2 for 90 min in the treatment of pseudomyxoma peritonei from perforated epithelial mucinous tumours of the appendix (HIPEC-PMP): protocol for a single-blinded, randomised controlled trial
AU - Sean Ewings
AU - Sophia Stanford
AU - Chris Wignall
AU - Karen Martin
AU - Pavel Mozgunov
AU - Gianmarco Caruso
AU - Louise Holmes
AU - Paul Smith
AU - David Scott
AU - Gareth Griffiths
AU - Alexios Tzivanakis
AU - Sanjeev Dayal
AU - Vasanth Mark Samuel
AU - Gui Han Lee
AU - Brendan Moran
AU - Faheez Mohamed
AU - Tom Cecil
PY - 2026
DA - 2026/11/03
JO - BMJ Open Gastroenterology
DO - 10.1136/bmjgast-2025-002187
UR - https://doi.org/10.1136/bmjgast-2025-002187
AB - Introduction: Pseudomyxoma peritonei (PMP) is a rare malignancy usually originating from a perforated appendix tumour. Potentially curative treatment involves cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy, commonly mitomycin-C (MMC). Different regimens of MMC are used across the world, with little convincing evidence for which regimen best balances favourable clinical outcomes against side effects and cost. The aim of this trial is to compare two dosing regimens of MMC during CRS. Methods and analysis: The HIPEC-PMP trial is an individually randomised, parallel group, single-blind, non-inferiority trial that will randomise patients (1:1) with PMP who are amenable to complete cytoreduction to one of two established regimens, either low-dose MMC (10 mg/m2 for 60 min) or high-dose MMC (35 mg/m2 for 90 min) to test the non-inferiority of low-dose MMC. A Bayesian design is used to incorporate prior information on each dose, with a principled approach to discount historical data if it is markedly different from the trial data. Participants must have a clinical and/or radiological diagnosis of PMP from a primary mucinous epithelial tumour of the appendix that is amenable to complete cytoreduction and will be recruited from a single specialist centre. Participants will be followed up for a minimum of 2 years. The primary endpoint is disease-free survival at 2 years, and secondary endpoints are overall survival, adverse events, quality of life and cost-effectiveness. A Bayesian analysis will be used to determine the probability that 2-year recurrence rates are within 10% to determine non-inferiority. The trial has a target sample size of 176. Ethics and dissemination: The study is sponsored by the University of Southampton, coordinated by the Cancer Research UK Southampton Clinical Trials Unit, and open to recruitment at the Peritoneal Malignancy Unit at the Hampshire Hospitals Foundation Trust. The trial protocol has received the favourable opinion of the London-Westminster Research Ethics Committee (REC 24/LO/0692), as well as the necessary approvals from the Medicines and Healthcare products Regulatory Agency and NHS Health Research Authority. Informed consent is required before any trial specific procedures are undertaken. It is intended that the results of the study will be disseminated via publication in peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. Trial registration number: NCT06513065.
SN - 2054-4774
ER -