The IPa-Gastric trial: Comparing Intraperitoneal Paclitaxel and Systemic Therapy versus Systemic Therapy alone in Gastric Cancer Patients with Peritoneal Metastasis

Prior treatment

• Comorbidity that does not allow treatment with ST or IP paclitaxel.
• Confirmed or suspected severe abdominal adhesions, for example after previous abdominal surgery, which do not allow effective IP paclitaxel treatment.
• Previously received more than 2 cycles of palliative-intent systemic chemotherapy (with the specific exception of cytology positive patients without manifest peritoneal metastases) for the current cancer disease.

Other illness

• Gastric cancer peritoneal reccurence which is diagnosed within 6 months after curative intent surgery (patients with recurrence diagnosed 6 months or more after curative intent surgery may be included).
• Severe coagulation disorder which precludes surgical interventions such as staging laparoscopies and SIPC placement
• Another malignancy that can affect survival within the next three years.
• Known or suspected allergies against any product included in the trial interventions.

Other

• Ongoing or recent participation (within 30 days) in a clinical trial with an investigational medicinal product.
• Distant metastases (including M1 lymph node mestastases according to AJCC 8th edition TNM classification) other than peritoneal, with the specific exception of ovarian, which are permitted.
• Symptomatic ascites already requiring drainage for palliation, or expected to require drainage in the short term, i.e within the next three weeks (radiological ascites without significant symptoms is acceptable).
• Known DPYD deficiency (including complete and partial deficiency).
• Known MSI-H/dMMR phenotype.
• Pregnancy or recent delivery within 28 days postpartum or ongoing breastfeeding.
• Active sex-life without use of secure contraceptive method.
• If the investigator considers the patient inappropriate for participation in the study for whatever reason.

• Gastric or gastro-oesophageal junction Siewert type II or III adenocarcinoma verified by biopsy or cytology from the primary tumour
• Adequate renal function (serum creatinine within1.5x of the upper limit of normal or Glomerular Filtration Rate via Cockcroft-Gault Formula>50mL.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Age of at least 18 years.
• 6.7. To compare time from randomisation to the first clinical or radiological evidence of small or large bowel obstruction between the two treatment groups
• Life expectancy of at least three months.
• Male participants are eligible to participate if they agree to the following requirements during the intervention period and for at least 6 months after the last dose of study intervention, which corresponds to the time needed to eliminate reproductive safety risk of the study intervention(s) plus an additional 90 days (a spermatogenesis cycle): o Refrain from donating sperm. PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR • Must agree to use contraception/barrier as detailed below. • Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. • Use of an additional highly effective contraceptive method with a failure rate of <1% per year for a female partner of childbearing potential.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: • Is not a WOCBP. OR • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for at least 9 months after the last dose of study intervention, which corresponds to the time needed to eliminate any reproductive safety risk of the study intervention(s). As for participants using a highly effective method that is user dependent, this contraception method must be used together with a second effective method of contraception. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• Peritoneal metastasis verified by biopsy, or cytology from ascites or peritoneal wash fluid
• Staging laparoscopy with assessment of peritoneal cancer index (PCI) performed less than four weeks before enrolment.
• Patients with tumour positive cytology (CYT+) without clinically manifest peritoneal metastases at baseline (PCI 0) staging laparoscopy can be included if they persist to be CYT+ after at least four cycles of systemic chemotherapy.
• Adequate bone marrow function (neutrophil count >1500/mm3, hemoglobin >8.0 g/dl and platelet count >100 000/mm3).
• Adequate liver function (bilirubin within 1.5x of the upper limit of normal, AST/ALT within 3x of upper limit of normal).