The PIPAC NAL-IRI study is designed to examine the maximal tolerated dose of nanoliposomal irinotecan (Nal-IRI, Onivyde) administered with repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC), in a monocentric, phase I trial.
Biopsy proven cancer of the pancreas, gallbladder or biliary tract, stomach, small bowel, colon, rectum, or appendix with extensive or irresectable peritoneal carcinomatosis
Estimated life expectancy > 6 months; > 3 months if primary cancer is pancreatic
Age ≥ 18 years
Adequate performance status (Karnofsky index > 60% and WHO performance status < 2)
Concomitant systemic (IV) treatment with irinotecan (either as monotherapy or as part of a combination regimen such as FOLFIRI, CAPIRI, or FOLFOXIRI)
Pregnancy or breastfeeding during the clinical study
Patients of childbearing age unable or unwilling to provide effective contraception during the study and until the end of relevant exposure (extended by 30 days (female participants) or 120 days (male participants) since the IMP is genotoxic).
Known allergy or intolerance to irinotecan
Sequential
PIPAC with Nal-IRI
DrugNanoliposomal irinotecan (Nal-IRI, Onivyde) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 30 to 90 mg/m². PIPAC will be performed every 4 to 6 weeks for 3 cycles.
Maximally tolerated dose (MTD) of Nal-IRI
Dose limiting toxicities will be monitored.
Recommended phase 2 dose
Define the dose recommended to use in a follow-up phase 2 trial based on incidence of DLT and toxicity data scored with CTCAE v5.0 for chemotherapy related toxicity.
Surgical morbidity will be measured
This will be estimated with the Dindo-Clavien classification and the comprehensive complication index (CCI).
Maximum concentration (Cmax) of nanoliposomal irinotecan
Determined for CPT-11, SN-38 and SN-38G in plasma and tumor tissue using UPLC-MS/MS.
Time to reach maximum concentration (Tmax) of nanoliposomal irinotecan
Determined for CPT-11, SN-38 and SN-38G in plasma and tumor tissue using UPLC-MS/MS.
Exploratory outcome: DNA topoisomerase I (TOP-1) gene copy number
This will be determined in plasma and tissue samples. This outcome evaluates anti-cancer efficacy.
Exploratory outcome: Expression of human carboxylesterase 2 (hCE2)
This will be determined in plasma and tissue samples. This outcome evaluates conversion of CPT-11 to SN-38 between patients.
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