Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC) in the management of cancers of the colon, ovary and stomach: a randomised controlled phase II trial of efficacy in peritoneal metastases

Research Question: Can PIPAC improve peritoneal progression free survival in peritoneal metastases (PM) from colorectal, ovarian and stomach cancers whilst maintaining or improving patient quality of life? Background: Peritoneal metastases represent a significant unmet clinical need and there is an urgent need for improved treatments for these poor prognosis patient groups. A novel anti-cancer technology is Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC). PIPAC aims to improve target specificity of anti-cancer therapies such as chemotherapy by delivering the medication directly to the PM. Chemotherapy is delivered as an aerosol into the closed abdominal cavity at conventional laparoscopy. It is suggested that the small size of the droplets under the raised intraperitoneal pressure utilised during laparoscopy drives the chemotherapy directly into the tumour nodules. PIPAC may be highly acceptable to patients due to the reduced systemic side effects as a result of poor peritoneal absorption. Aims: To a) generate high-quality evidence regarding the efficacy of PIPAC in the treatment of PM from colorectal, ovarian and stomach cancer compared to standard of care alone and b) create a bespoke PM quality of life measurement for trials of peritoneal disease interventions Objectives: To determine if PIPAC given with (colorectal, stomach) or instead of (ovarian) systemic anti-cancer therapy (SACT) improves peritoneal PFS compared to standard SACT. To generate data that can be used in isolation and in combination with other studies through meta-analysis to inform future research and practice. To determine how PIPAC impacts quality of life compared to standard of care. To determine the safety of PIPAC. To determine the proportion of patients who complete a course of 3 cycles of PIPAC treatment. Sub-study objectives: To determine the patient related outcomes relevant to PM and identify the methods of measuring those outcomes. To develop a bespoke PM specific quality of life measurement for a definitive trial in this field. Methods: This is a basket trial with a master protocol covering the overarching research methodology and separate trial protocol, sample size and analysis plan for each cancer type involved. Patients will be identified through clinicians at PIPAC centres and local referring centres. Recruiting clinicians will log onto a central web-based platform, to allocate eligible patients in a 1:1 ratio to either standard of care or PIPAC. Patients will be allocated to trial groups separately for each cancer type. The primary outcome measure will be peritoneal PFS as measured by the RECIST criteria on CT scan. Timelines for delivery: The trial will start in November 2022 and will run for 4 years. Anticipated Impact and Dissemination: This phase II study of PIPAC will provide high quality randomised controlled data to confirm or refute suggestions of efficacy from international case series. It will utilise the unique opportunity provided to determine which outcomes are important to patients and importantly how to measure those factors to improve this and future trials