Intraperitoneal Aerosolized Nanoliposomal Irinotecan (Nal-IRI) in Peritoneal Carcinomatosis From Gastrointestinal Cancer

NCT ID: NCT05277766

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-21
• Study Completion Date: 2027-04-30

Brief Summary

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.

Detailed Description

Peritoneal metastases (PM) are a common manifestation of gastrointestinal cancer. The prognosis of patients with PM is particularly poor, and response to systemic chemotherapy is worse compared to parenchymal metastatic cancer in the liver or lungs. In addition, patients with PM frequently develop debilitating symptoms such as intractable ascites, bowel obstruction, or ureteric obstruction, resulting in a severely compromised quality of life.

In selected patients with widespread PM, pressurized intraperitoneal aerosol chemotherapy (PIPAC) holds considerable promise. Briefly, PIPAC combines laparoscopy with intraperitoneal (IP) administration of chemotherapy as an aerosol, which is generated by a nebulizer. The pharmacokinetic (PK) and clinical advantages of PIPAC may be further enhanced by using nanosized anticancer drugs. Nal-IRI (Onivyde) is a nanoliposomal formulation of irinotecan (Camptothecin-11 (CPT-11)), with a markedly superior efficacy when compared with free CPT-11 in human breast and colon cancer xenograft models.

This is a phase I clinical study with aerosolized IP Nal-IRI in patients with PM from GI cancer. In this phase I study, dose escalation will be combined with pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.

Conditions

Peritoneal Carcinomatosis; Peritoneal Metastases; Colorectal Cancer; Small Bowel Cancer; Appendix Cancer; Gastric Cancer; Pancreatic Cancer; Bile Duct Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nal-IRI (Onivyde) - 30mg/m²

PIPAC with Onivyde (30 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Group Type: EXPERIMENTAL

PIPAC with Nal-IRI

Intervention Type: DRUG

Nanoliposomal 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.

Nal-IRI (Onivyde) - 45mg/m²

PIPAC with Onivyde (45 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Group Type: EXPERIMENTAL

PIPAC with Nal-IRI

Intervention Type: DRUG

Nanoliposomal 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.

Nal-IRI (Onivyde) - 60mg/m²

PIPAC with Onivyde (60 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Group Type: EXPERIMENTAL

PIPAC with Nal-IRI

Intervention Type: DRUG

Nanoliposomal 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.

Nal-IRI (Onivyde) - 75mg/m²

PIPAC with Onivyde (75 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Group Type: EXPERIMENTAL

PIPAC with Nal-IRI

Intervention Type: DRUG

Nanoliposomal 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.

Nal-IRI (Onivyde) - 90mg/m²

PIPAC with Onivyde (90 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Group Type: EXPERIMENTAL

PIPAC with Nal-IRI

Intervention Type: DRUG

Nanoliposomal 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.

Interventions

PIPAC with Nal-IRI

Nanoliposomal 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.

Intervention Type: DRUG

Other Intervention Names

Onivyde

Eligibility Criteria

Inclusion Criteria

• 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)
• Written informed consent obtained prior any act of the research

Exclusion Criteria

• 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
• Significant amount of ascites detectable (exceeding 3l in volume)
• Intestinal or urinary tract obstruction
• Extensive hepatic and/or extra-abdominal metastatic disease
• Impaired renal function (serum creatinine > 1.5 mg/dl or calculated GFR (CKD-EPI) < 60 mL/min/1.73 m²
• Impaired liver function (serum total bilirubin > 1.5 mg/dl, except for known Gilbert's disease)
• Platelet count < 100.000/µl
• Hemoglobin < 9g/dl
• Neutrophil granulocytes < 1.500/ml
• Patients known to use:

• CYP3A4 inducers (rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St John's wort)
• inhibitors of CYP3A4 (clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 (atazanavir, gemfibrozil, indinavir, regorafenib)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kom Op Tegen Kanker

OTHER

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wim P Ceelen, MD, PhD, Prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

UZ Ghent

Ghent, East-Flanders, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Wim P Ceelen, MD, PhD, Prof

Role: CONTACT

wim.ceelen@ugent.be

+3293326251

Facility Contacts

Wim P Ceelen, MD, PhD, Prof

Role: primary

wim.ceelen@ugent.be

+3293326251

Wouter Willaert, MD, PhD, Prof

Role: backup

wouter.willaert@ugent.be

+3293328950

Other Identifiers

ONZ-2022-0120

Identifier Type: -

Identifier Source: org_study_id