NCT05277766

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
11mo left

Started Nov 2022

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Nov 2022Apr 2027

First Submitted

Initial submission to the registry

February 18, 2022

Completed
24 days until next milestone

First Posted

Study publicly available on registry

March 14, 2022

Completed
8 months until next milestone

Study Start

First participant enrolled

November 21, 2022

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Expected
Last Updated

July 1, 2025

Status Verified

June 1, 2025

Enrollment Period

3.1 years

First QC Date

February 18, 2022

Last Update Submit

June 26, 2025

Conditions

Peritoneal CarcinomatosisPeritoneal MetastasesColorectal CancerSmall Bowel CancerAppendix CancerGastric CancerPancreatic CancerBile Duct Cancer

Keywords

PIPACNal-IRIPeritoneal carcinomatosisdose-finding studypharmacokineticspharmacodynamicssafety and efficacyOnivydePrimary gastrointestinal cancerColorectal cancerSmall bowel cancerAppendix cancerStomach cancerPancreatic cancerCholangiocarcinomadose-escalation studyPeritoneal metastases

Outcome Measures

Primary Outcomes (1)

  • Maximally tolerated dose (MTD) of Nal-IRI

    Dose limiting toxicities will be monitored.

    Within 14 weeks of the start of the treatment

Secondary Outcomes (16)

  • Recommended phase 2 dose

    6 months after last subject's third PIPAC

  • Surgical morbidity will be measured

    6 months after third PIPAC

  • Maximum concentration (Cmax) of nanoliposomal irinotecan

    Plasma at 10 timepoints: T= pre-dose (0 minutes=start nebulization), T=30 minutes, T=1.5 hour, T=2.5 hours, T=6 hours, T=24 hours, T=72 hours, T=168 hours, T=336 hours, T=504 hours // Tissue: T= pre-dose (0 minutes=start nebulization), T = 30 minutes

  • Time to reach maximum concentration (Tmax) of nanoliposomal irinotecan

    Plasma at 10 timepoints: T= pre-dose (0 minutes=start nebulization), T=30 minutes, T=1.5 hour, T=2.5 hours, T=6 hours, T=24 hours, T=72 hours, T=168 hours, T=336 hours, T=504 hours // Tissue: T= pre-dose (0 minutes=start nebulization), T = 30 minutes

  • Area under the curve (AUC0h-24h) of nanoliposomal irinotecan

    Plasma at 10 timepoints: T= pre-dose (0 minutes=start nebulization), T=30 minutes, T=1.5 hour, T=2.5 hours, T=6 hours, T=24 hours, T=72 hours, T=168 hours, T=336 hours, T=504 hours // Tissue: T= pre-dose (0 minutes=start nebulization), T = 30 minutes

  • +11 more secondary outcomes

Other Outcomes (2)

  • Exploratory outcome: DNA topoisomerase I (TOP-1) gene copy number

    8 months after last subject last visit

  • Exploratory outcome: Expression of human carboxylesterase 2 (hCE2)

    8 months after last subject last visit

Study Arms (5)

Nal-IRI (Onivyde) - 30mg/m²

EXPERIMENTAL

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

Drug: PIPAC with Nal-IRI

Nal-IRI (Onivyde) - 45mg/m²

EXPERIMENTAL

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

Drug: PIPAC with Nal-IRI

Nal-IRI (Onivyde) - 60mg/m²

EXPERIMENTAL

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

Drug: PIPAC with Nal-IRI

Nal-IRI (Onivyde) - 75mg/m²

EXPERIMENTAL

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

Drug: PIPAC with Nal-IRI

Nal-IRI (Onivyde) - 90mg/m²

EXPERIMENTAL

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

Drug: PIPAC with Nal-IRI

Interventions

PIPAC with Nal-IRIDRUG

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.

Also known as: Onivyde
Nal-IRI (Onivyde) - 30mg/m²Nal-IRI (Onivyde) - 45mg/m²Nal-IRI (Onivyde) - 60mg/m²Nal-IRI (Onivyde) - 75mg/m²Nal-IRI (Onivyde) - 90mg/m²

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UZ Ghent

Ghent, East-Flanders, 9000, Belgium

RECRUITING

MeSH Terms

Conditions

Peritoneal NeoplasmsColorectal NeoplasmsAppendiceal NeoplasmsStomach NeoplasmsPancreatic NeoplasmsBile Duct NeoplasmsCholangiocarcinoma

Interventions

irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Abdominal NeoplasmsNeoplasms by SiteNeoplasmsDigestive System NeoplasmsDigestive System DiseasesPeritoneal DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesCecal NeoplasmsCecal DiseasesStomach DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System DiseasesBiliary Tract NeoplasmsBile Duct DiseasesBiliary Tract DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Study Officials

  • Wim P Ceelen, MD, PhD, Prof

    University Hospital, Ghent

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Wim P Ceelen, MD, PhD, Prof

CONTACT

+3293326251wim.ceelen@ugent.be

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Phase I study with dose escalation according to two-stage time-to-event continual reassessment method (TITE-CRM): 3x30 - 3x45 - 4x60 - 4x 75 - 16x90 mg/m2 (number of patients x assigned dose). Dose escalation is continued until dose-limiting toxicity (DLT) is observed. Only DLTs that take place within 14 weeks of the start of the treatment are considered. From that moment, TITE-CRM updates an initial prior estimate of the probabilities of DLT based on all available information, including patients with incomplete follow-up. Newly accrued patients are assigned the dose whose estimated probability of DLT at that time is closest to target probability. This method allows for continuous, staggered accrual of patients. The target-probability of DLT is 30%. The estimated MTD will be the dose whose estimated posterior probability of DLT is closest to that targeted probability.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 18, 2022

First Posted

March 14, 2022

Study Start

November 21, 2022

Primary Completion

January 1, 2026

Study Completion (Estimated)

April 1, 2027

Last Updated

July 1, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

Locations

BE(1)