Table 1:

Secondary endpoints.

Objectives	Endpoints
Feasibility	–Number of patients unable to undergo six cycles of systemic chemotherapy combined with three PIPAC cycles and reasons for discontinuation –Number of patients who discontinued or postponed beyond 10 days the scheduled standard systemic chemotherapy after each PIPAC cycle –Number of patients that reduce the dose of systemic chemotherapy during the study –Number of patients that reduce the dose of PIPAC drug during the study
Safety	–Number of patients with major toxicity, defined as grade ≥3 according to CTCAE v5.0 during the on-study evaluation phase and up to four weeks after the last chemotherapy administration –Number of patients with minor toxicity, defined as grade ≤2 according to CTCAE v5.0 during the treatment period and up to 4 weeks after the last combined course –Number of patients with major and minor postoperative complications, defined as grade ≥3 and grade ≤2 according to Clavien-Dindo, respectively, during the treatment period and up to 4 weeks after the last PIPAC procedure –Hospital stays, which is defined as the number of days between PIPAC and initial discharge –Number of readmissions, defined as any hospital admission after discharge, up to four weeks after the last PIPAC procedure
Antitumor activity	–Pathological tumor response, based on the review of peritoneal biopsies collected during each PIPAC, performed by a pathologist blinded to clinical outcomes using the PRGS. A patient will be considered a responder if any reduction in the PRGS during subsequent biopsies will be recorded –Macroscopic tumor response, based on PCI and ascites volume recorded during each PIPAC –Biochemical tumor response, based on tumor markers (CEA, Ca 19.9, Ca 125) measured at different time points –Quality of life of the population will be assessed through the potential changes in QoL scores extracted from the questionnaire QLQ-C30 at different time points – PFS defined as the time between treatment start and one of the following events, whichever comes first: – Radiologic progression based on RECIST criteria v. 1.1 – Clinical progression (i.e., bowel occlusion, inability to oral feeding, refractory ascites) – Death – The OS is defined as the time between treatment start and death

PIPAC, Pressurized Intraperitoneal Aerosol Chemotherapy; CTCAE, Common Terminology Criteria for Adverse Events; PRGS, Peritoneal Regression Grading Score; PCI, Peritoneal Cancer Index; QoL, quality of live; QLQ-30, Quality of Life Questionnaire; PFS, Progression-Free Survival; OS, Overall Survival.