Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Multimodal Therapy for Patients with Oligometastatic Peritoneal Gastric Cancer: a Randomized Multicenter Phase III Trial: PIPAC_VEROne

This is a prospective, open label, randomized multicenter phase III clinical study that aims to evaluate the effects of PIPAC combined with systemic chemotherapy vs. intravenous systemic chemotherapy alone on patients with gastric cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastasis (PCI ≤ 6). Patients will be randomly assigned in a 1:1 ratio to Arm A: intravenous chemotherapy (FOLFOX) vs. Arm B: intravenous chemotherapy (FOLFOX) plus PIPAC with cisplatin and doxorubicin.

Patients eligible for the trial must have performed: diagnostic upper intestinal endoscopy with biopsies, thoraco-abdominal-pelvic CT scan, laboratory exams: serum CEA, CA19.9, hemoglobin, leukocytes, neutrophils, platelets, glycemia, AST, ALT, LDH, total bilirubin, alkaline phosphatase, serum albumin, total protein, plasmatic APTT, PT, creatinine clearance and serum creatinine and pregnancy serological test.

Patients should undergo to staging laparoscopy in one of the participating centers to define the peritoneal involvement. After that peritoneal metastasis will be confirmed by cytological/histopathological final examination and after receiving the written informed consent, patient will be randomized.

Once the inclusion and exclusion criteria are confirmed, each patient will be randomized in a 1:1 ratio (Chemotherapy alone vs chemotherapy plus PIPAC) to blocks of 14 using a centralized randomization list, stratified by center. Randomization list will be managed by the Medical Epidemiology and Statistics Unit, Department of Diagnostics and Public Health of the University of Verona. This list will be built using the Biostatistics Unit of the University of Verona using software (www.randomizer.org) Patients randomized in the Arm A will undergo to 6 courses of systemic chemotherapy according to FOLFOX regimen, after these six courses of chemotherapy, radiologic restaging (CT scan) as well as a second staging laparoscopy will be performed. If a Progression Disease will be detected, the patient will end the trial and will undergo to II line chemotherapy regimen. If a stable disease or a partial response will be documented, after a multidisciplinary discussion, patient will undergo to either further 6 courses of chemotherapy or to cytoreductive surgery plus HIPEC.

Patients randomized in the ARM B will undergo to 6 courses of systemic chemotherapy (FOLFOX regimen) plus PIPAC every two cycles of chemo. At least seven days should last between each PIPAC and the next chemotherapy course, and at least 14 days should last between the chemotherapy course and the next PIPAC. After six courses of chemotherapy and 3 PIPACs procedure, a radiologic restaging (CT scan) as well as a laparoscopic reassessment will be performed. If a Progression Disease will be detected, the patient will end the trial and will undergo to II line chemotherapy regimen. If a stable disease or a partial response will be documented, patient will be treated with cytoreductive surgery plus HIPEC.