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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
3 weekly IP irinotecan (max 6 cycles), dose via dose-escalation design as specified per arm.
Capecitabine 1000 mg/m2 twice daily day 1-14 (per os), and Oxaliplatin 130 mg/m2 on day 1 IV infusion.
Erasmus MC
Rotterdam, South Holland, Netherlands
Catharina Hospital
Eindhoven, Netherlands
Maximum-tolerated dose
The maximum tolerable dose and recommended phase II dose of intraperitoneal irinotecan added to systemic chemotherapy (capecitabine/oxaliplatin)
Time frame: 18 weeks
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.
Time frame: 18 weeks
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 These will be withdrawn at specific time-points, namely prior to infusion, at the end of the intraperitoneal infusion, ass well as 30 minutes, 1, 1.5, 2, 3, 4, 6, and 24 hours post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.
Time frame: 3 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.