Concomitant Intraperitoneal and Systemic Chemotherapy in Patients With Extensive Peritoneal Carcinomatosis of Gastric Origin

September 26, 2023 updated by: Prof. R.H.J. Mathijssen, MD, PhD, Erasmus Medical Center

Gastric cancer with peritoneal carcinomatosis has a poor prognosis, with little treatment options available. The current treatment strategy consists of palliative systemic chemotherapy. However, previous research suggests that systemic chemotherapy is less effective against peritoneal carcinomatosis than against metastases that spread hematogenously.

Several studies suggested that in patients with peritoneal carcinomatosis, intraperitoneal chemotherapy (IP) may be superior compared to intravenous chemotherapy. Intraperitoneal chemotherapy could lead to higher concentrations of chemotherapy in the peritoneal cavity for a longer period of time, resulting in an increased cumulative exposure to the peritoneal metastases. A few Asian studies have shown promising results with intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of gastric origin. However, intraperitoneal chemotherapy combined with systemic chemotherapy has not been investigated in Western patients with peritoneal carcinomatosis of gastric origin yet. The objective of this trial is to establish the maximum tolerated dose (MTD) of intraperitoneal administration of irinotecan, added to systemic capecitabine/oxaliplatin (CAPOX) in patients with peritoneal carcinomatosis of gastric origin.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
      • Eindhoven, Netherlands
        • Recruiting
        • Catharina Hospital
        • Contact:
        • Principal Investigator:
          • Geert-Jan Creemers, MD, PhD
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015 GD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a histologically confirmed diagnosis of HER2-negative gastric cancer.
  • A histologically confirmed diagnosis of peritoneal carcinomatosis.
  • Age ≥ 18 years old.
  • Written informed consent according to the ICH-GCP and national/local regulations.
  • A peritoneal cancer index (PCI) ≥7 evaluated by laparoscopy or laparotomy before inclusion in this trial.
  • Patients must be ambulatory: World Health Organisation (WHO) performance status 0 or 1.
  • Life expectancy of at least 3 months.
  • Ability to return to the Erasmus MC for adequate follow-up as required by this protocol.

  • Patients must have normal organ function and adequate bone marrow reserve as assessed by the following laboratory requirements:

    • absolute neutrophil count >1.5 * 10^9/l;
    • platelet count >100*10^9/l;
    • Hb>6.0mmol/l;
    • Bilirubin < 1.5x upper limit of normal (ULN);
    • Serum aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2.5 x ULN;
    • Glomerular Filtration Rate (GFR) >45 and Creatinine clearance <2 x ULN.

Exclusion Criteria:

  • Medical or psychological impediment to probable compliance with the protocol.
  • Serious concomitant disease or active infections.
  • Distant metastasis other than peritoneal metastasis or metastatic lymph nodes.
  • No sufficient oral food intake.
  • Polyneuropathy grade 2 or worse according to CTCAE version 5.0.
  • History of auto-immune disease or organ allografts, or with active or chronic infection, including HIV and viral hepatitis.
  • Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for participation in this study.
  • Homozygous UGT1A1*28 genotype.
  • Homozygous dihydropyrimidine dehydrogenase (DPYD) genotype (tested for *2A, *13, 2846A>T, and 1236G>A).
  • Current use of strong CYP3A4-inhibitors or inducers. If patients use this CYP3A4-modulating medication, it is allowed to stop it within 14 days of start of treatment.
  • Pregnant or lactating women.
  • Concomitant participation in a competing clinical study.
  • Absence of assurance of compliance with the protocol.
  • An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intraperitoneal irinotecan 50 mg + CAPOX
Intraperitoneal irinotecan, dose level 1 50 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Experimental: Intraperitoneal irinotecan 75 mg + CAPOX
Intraperitoneal irinotecan, dose level 2 75 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Experimental: Intraperitoneal irinotecan 100 mg + CAPOX
Intraperitoneal irinotecan, dose level 3 100 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Experimental: Intraperitoneal irinotecan 150 mg + CAPOX
Intraperitoneal irinotecan, dose level 4 150 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Experimental: Intraperitoneal irinotecan 200 mg + CAPOX
Intraperitoneal irinotecan, dose level 5 200 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Experimental: Intraperitoneal irinotecan 250 mg + CAPOX
Intraperitoneal irinotecan, dose level 6 250 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
Drug: Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Other Names:
  • Intraperitoneal irinotecan
Drug: CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose
Time Frame: 18 weeks
The maximum tolerable dose and recommended phase II dose of intraperitoneal irinotecan added to systemic chemotherapy (capecitabine/oxaliplatin)
18 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 18 weeks
Toxicity graded according to the CTCAE v.5.0 determined at every cycle by the medical oncologist. Toxicity will be summarized descriptively.
18 weeks
Area Under the Curve (AUC) ratio intraperitoneal/systemic irinotecan
Time Frame: 3 weeks
During the first irinotecan intraperitoneal cycle, pharmacokinetic measurements wil be obtained. These will be withdrawn at specific time-points, namely prior to infusion, at the end of the intraperitoneal infusion, ass well as 30 minutes, 1, 1.5, 2, 3, 4, 6, and 24 hours post infusion. Blood samples from a peripheral venous catheter and peritoneal fluid will be drawn from the peritoneal access port. We assume that the AUC of irinotecan and SN-38 follow a log-normal distribution. Therefore, the analysis will be performed on log-transformed data. The antilog will be taken from the ratio and corresponding 95% confidence interval boundaries will be reported.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasmus Medical Center

Investigators

  • Principal Investigator: Ron Mathijssen, Professor, Erasmus Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2022

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

April 25, 2022

First Submitted That Met QC Criteria

May 13, 2022

First Posted (Actual)

May 18, 2022

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL79619.078.21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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