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

NCT05379790 | Completed Phase 1

• 1 other identifier: NL79619.078.21
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Gastric Cancer; Peritoneal Metastases

Keywords

Peritoneal metastases; Gastric cancer; Intraperitoneal; Irinotecan

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose

  The maximum tolerable dose and recommended phase II dose of intraperitoneal irinotecan added to systemic chemotherapy (capecitabine/oxaliplatin)

  18 weeks

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  18 weeks

• Area Under the Curve (AUC) ratio intraperitoneal/systemic irinotecan

  3 weeks

Study Arms (6)

Intraperitoneal irinotecan 50 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 1 50 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Intraperitoneal irinotecan 75 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 2 75 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Intraperitoneal irinotecan 100 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 3 100 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Intraperitoneal irinotecan 150 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 4 150 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Intraperitoneal irinotecan 200 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 5 200 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Intraperitoneal irinotecan 250 mg + CAPOX

EXPERIMENTAL

Intraperitoneal irinotecan, dose level 6 250 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)

Drug: Irinotecan; Drug: CAPOX

Interventions

Irinotecan DRUG

3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.

Also known as: Intraperitoneal irinotecan

Intraperitoneal irinotecan 100 mg + CAPOX; Intraperitoneal irinotecan 150 mg + CAPOX; Intraperitoneal irinotecan 200 mg + CAPOX; Intraperitoneal irinotecan 250 mg + CAPOX; Intraperitoneal irinotecan 50 mg + CAPOX; Intraperitoneal irinotecan 75 mg + CAPOX

CAPOX DRUG

Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.

Intraperitoneal irinotecan 100 mg + CAPOX; Intraperitoneal irinotecan 150 mg + CAPOX; Intraperitoneal irinotecan 200 mg + CAPOX; Intraperitoneal irinotecan 250 mg + CAPOX; Intraperitoneal irinotecan 50 mg + CAPOX; Intraperitoneal irinotecan 75 mg + CAPOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (2)

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Catharina Hospital

Eindhoven, Netherlands

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Ron Mathijssen, Professor

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A classic phase I '3+3' dose-escalation study.

Study Record Dates

• First Submitted: April 25, 2022
• First Posted: May 18, 2022
• Study Start: May 25, 2022
• Primary Completion: November 25, 2024
• Study Completion: February 17, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)