Title: The PICCOS Trial (PIPAC in Cancers of the Colon, Ovaries and Stomach): A randomised controlled phase II trial in Colorectal, Ovarian and Stomach cancers to define the efficacy of Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC) in the management of peritoneal metastases.
Funder: Medical Research Council

Abstract: Aims Bowel, ovarian and stomach cancer often spreads (metastasises) to the lining (peritoneum) of the abdominal cavity. This trial aims to determine if a new way of delivering chemotherapy as a spray, directly into the peritoneal cavity, might improve survival in patients with peritoneal metastases, compared to conventional intravenous chemotherapy. Critically, we will also assess the impact of treatment on patient quality of life. Background Up to 13%, 50% and 14% of patients with bowel, ovarian and stomach cancer respectively, present with peritoneal metastases. When this form of spread occurs, patients are normally told their disease is incurable. As well as a relatively rapid decline, peritoneal metastases can cause a series of unpleasant symptoms due to new tumour growth. Peritoneal metastases are difficult to treat with conventional anti-cancer drugs and there is an urgent need to develop new treatment strategies. A new strategy showing potential is Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC). PIPAC delivers anti-cancer drugs into the peritoneal cavity as an aerosol during keyhole surgery. PIPAC has been shown to deliver higher doses of chemotherapy directly to tumour sites compared to conventional treatment, with fewer side-effects due to less chemotherapy circulating in the blood. PIPAC has been shown to be both safe and feasible in a series of clinical trials. The question that now remains is whether PIPAC is efficacious or not. The National Institute for Clinical Excellence has recommended that PIPAC should only be offered to UK patients within a research trial setting. There are trials for patients in Europe but not in the UK. Design and Methods This randomised controlled trial will be open to patients with bowel, ovarian or stomach cancer. Each cancer type will have individual eligibility criteria and protocols to allow for the necessary variations in treatment. In all cancer types, patients will be randomised to receive either standard chemotherapy delivered via the bloodstream or a course of chemotherapy, in which a proportion of the treatment will be delivered using PIPAC. This study design enables the variation required to include patients with different cancer types and also, the ability to stop the trial for any one cancer type if it is not working whilst continuing with the others. Patient and Public involvement Patients in the UK are aware of PIPAC treatment with specialists frequently approached by patients and carers requesting it. This has been a driving force in developing this trial. Patients have been involved from an early stage and helped to determine acceptable time points for investigations, design travel policies, select the best quality of life assessment tools, define the priority of research questions and write the proposal to this point. They will continue to support study design, raise trial awareness and ensure patient concerns and well-being are given paramount importance going forwards. Dissemination PIPAC has excited much interest in patient groups. We will disseminate study results through social media, relevant charitable organisations, presentation at academic conferences, peer-reviewed journals as well as through the trial web page hosted at the Centre for Trials Research. Information leaflets, public presentations and media coverage are integral elements of our public engagement plans. The results will strongly influence a future NICE review of PIPAC in the UK.

Lay abstract: 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

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS