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

Primary Purpose

Gastric Cancer, Peritoneal Metastases

Status

Recruiting

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

Irinotecan

CAPOX

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring Peritoneal metastases, Gastric cancer, Intraperitoneal, Irinotecan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Erasmus MCRecruiting
Catharina HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Intraperitoneal irinotecan 50 mg + CAPOX

Intraperitoneal irinotecan 75 mg + CAPOX

Intraperitoneal irinotecan 100 mg + CAPOX

Intraperitoneal irinotecan 150 mg + CAPOX

Intraperitoneal irinotecan 200 mg + CAPOX

Intraperitoneal irinotecan 250 mg + CAPOX

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Maximum-tolerated dose

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

Secondary Outcome Measures

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

Toxicity graded according to the CTCAE v.5.0 determined at every cycle by the medical oncologist. Toxicity will be summarized descriptively.

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

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.

Full Information

NCT ID

NCT05379790

First Posted

April 25, 2022

Last Updated

September 26, 2023

Sponsor

Erasmus Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT05379790

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 25, 2022 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastric Cancer, Peritoneal Metastases

Keywords

Peritoneal metastases, Gastric cancer, Intraperitoneal, Irinotecan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intraperitoneal irinotecan 50 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Arm Title

Intraperitoneal irinotecan 75 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Arm Title

Intraperitoneal irinotecan 100 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Arm Title

Intraperitoneal irinotecan 150 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Arm Title

Intraperitoneal irinotecan 200 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Arm Title

Intraperitoneal irinotecan 250 mg + CAPOX

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Other Intervention Name(s)

Intraperitoneal irinotecan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

CAPOX

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum-tolerated dose

Description

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

Time Frame

18 weeks

Secondary Outcome Measure Information:

Title

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

Description

Toxicity graded according to the CTCAE v.5.0 determined at every cycle by the medical oncologist. Toxicity will be summarized descriptively.

Time Frame

18 weeks

Title

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

Description

Time Frame

3 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Niels Guchelaar

Phone

+31 10 70 39640

n.guchelaar@erasmusmc.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ron Mathijssen, Professor

Organizational Affiliation

Erasmus Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Erasmus MC

City

Rotterdam

State/Province

Zuid-Holland

ZIP/Postal Code

3015 GD

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Niels Guchelaar

Phone

0107039640

n.guchelaar@erasmusmc.nl

Facility Name

Catharina Hospital

City

Eindhoven

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marion Welten, MD

Phone

+31402395995

marion.welten@catharinaziekenhuis.nl

First Name & Middle Initial & Last Name & Degree

Geert-Jan Creemers, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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