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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05379790
• Other study ID #: NL79619.078.21
• Status: Recruiting
• Phase: Phase 1
• Start date: May 25, 2022
• Est. completion date: August 2024

Study information

• Verified date: September 2023
• Source: Erasmus Medical Center
• Contact: Niels Guchelaar
• Phone: +31 10 70 39640
• Email: n.guchelaar[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Gastric Cancer
• Neoplasm Metastasis
• Peritoneal Metastases
• Peritoneal Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• Irinotecan
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
• CAPOX
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.

Locations

Country	Name	City	State
Netherlands	Catharina Hospital	Eindhoven
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose	The maximum tolerable dose and recommended phase II dose of intraperitoneal irinotecan added to systemic chemotherapy (capecitabine/oxaliplatin)	18 weeks
Secondary	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.	18 weeks
Secondary	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.	3 weeks