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
Colorectal, ovarian and stomach cancer with peritoneal metastasis
Current interventions as of 19/06/2025: The trial will test a new method to deliver chemotherapy as a spray, directly into the peritoneal cavity, to determine whether this improves survival in patients with peritoneal metastases, compared to conventional intravenous chemotherapy. 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 combination of standard chemotherapy (SACT) and/or Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC), where three PIPAC procedures are performed (ovarian intervention arm receives PIPAC with no SACT). This trial design enables the variation required to include patients with different cancer types and the ability to stop the trial for any one cancer type if it is not working, whilst continuing with the others. Prior to randomisation, the treating Investigator will select the SACT regimen most appropriate to the individual patient from treatment options available for the patient’s disease group. Following randomisation, treatment will commence within two weeks for all participants other than those in the ovarian intervention arm, for whom the first PIPAC should take place within three weeks. There is no trial-specific drug provision; all drugs used in the trial will be taken from local hospital supplies. Each disease group has specific options for the chemotherapy dose and frequency, which we have represented in our protocol with 3 separate schemas and tables for treatment options (these can be viewed in the attached synopsis). All participants will be followed up to the point of peritoneal disease progression or a minimum of six months post-randomisation, whichever comes first. Ongoing assessments will end for all patients when the last pati
Current key inclusion criteria as of 01/04/2026: All disease groups: 1. 16 years and older 2. Visible (measurable or non-measurable) peritoneal lesion(s) on computerised tomography (CT) imaging as per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 3. Eastern Cooperative Oncology Group (ECOG) performance status 0–1 4. Adequate bone marrow, liver and kidney function (within 7 days prior to randomisation): 4.1. Neutrophil ≥1.5×10"9/L 4.2. White blood cells ≥3.0 x 10"9/L 4.3. Platelets ≥100×10"9/L 4.4. Haemoglobin ≥90 g/l 4.5. Serum bilirubin <30 micromol/L 4.6. ALT/AST ≤2.5 x ULN (if both done, both must meet criteria) 4.7. Creatinine clearance ≥50 ml/min (Creatinine clearance should be estimated using the online ClinCalc calculator: https://clincalc.com/kinetics/crcl.aspx) 5. Fit enough to receive full dose of systemic anti-cancer therapy (SACT) in cycle 1 as defined in the protocol. 6. Ability to provide informed consent obtained prior to any trial-specific screening procedures. Colorectal group only: 1. Peritoneal Metastasis (PM) from MDT confirmed primary adenocarcinoma (this may include “suspicious” if agreed by MDT) of the colorectum or appendiceal cancer (not pseudomyxoma). Ovarian group only: 1. PM from MDT confirmed primary epithelial ovarian, tubal, or primary peritoneal platinum-resistant carcinoma (including clinical recurrence, refractory disease, or persistent disease within 6 months of last chemotherapy). (This may include “suspicious” if agreed by MDT). Stomach group only: 1. PM from histologically proven primary adenocarcinoma (any subtype) of stomach or Siewert type 3 gastro-oesophageal junction tumour (any Human Epidermal Growth Factor Receptor 2 [HER2] status or Combined Positive Score [CPS]). _____ Previous participant inclusion criteria as of 19/06/2025: All disease groups: 1. 16 years and older 2. Visible (measurable or non-measurable) peritoneal lesion(s) on computerised tomography (CT) imaging as per Response Evaluation Cri
Current key exclusion criteria as of 01/04/2026: All disease groups: 1. Any prior malignancy not considered in complete remission for at least 2 years, excluding non-melanoma skin cancer 2. Pregnant or breastfeeding 3. Untreated central nervous system disease or symptomatic central nervous system metastasis, history, or evidence of thrombotic or haemorrhagic disorders not considered currently in complete remission 4. Contraindication to any drug contained in the chemotherapy regimen 5. Medical, geographical, sociological, psychological, or legal conditions that would prevent the patient from completing the study or signing the informed consent 6. Unresolved bowel obstruction or parenteral nutrition or gastric tube 7. Contraindication to surgery 8. Participating in other oncological trials that may impact on endpoint 9. Life expectancy <3 months *Note a minimum of 4 weeks washout between date of PIPAC 1 and last dose of bevacizumab / aflibercept (if applicable) must be complied with should a patient be randomised to the intervention arm. Colorectal group only: 1. Extra-peritoneal metastases except for: 1.1. Retroperitoneal lymph nodes <2cm 1.2. Lung metastases; with < 5 lung metastases none >1cm 1.3. Solid organ metastases deemed asymptomatic and non-progressive by MDT 2. Eligible for and chooses cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) upfront 3. Dihydropyrimidine Dehydrogenase Deficiency (DPYD) variant detected 4. Microsatellite instability (MSI) high or MMR-deficient (unless progressed on immunotherapy) 5. Previous cytoreductive surgery (CRS) or Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and felt to be surgically suitable by MDT Ovarian group only: 1. Extra-peritoneal metastases (with the exception of retroperitoneal lymph nodes) 2. Parenchymal liver or spleen metastases 3. Malignant pleural effusion 4. Non-epithelial pathology subtype 5. Peritoneal disease, amenable to surgical resection Stomach group only: 1.