This study is a prospective, multi-center, open-label phase I trial designed to determine the maximun tolerated dose of IP oxaliplatin when given in combination with mFOLFIRI.
This study is a prospective, multi-center, open-label phase I trial designed to determine the MTD of IP oxaliplatin when given in combination with mFOLFIRI. This will be conducted according to a traditional 3+3 dose-escalation schedule and halted once MTD is established. After consent and once deemed eligible for trial participation, patients will receive four cycles of study therapy. During therapy, patients will be monitored for dose-limiting toxicities and adverse events. After completion of all four cycles patients will be followed until resolution of any ongoing study treatment-related adverse events, initiation of alternative treatment, and survival. Study drug treatment will be administered on day one of a 14-day cycle and the DLT evaluation period will be defined as the first three cycles of combination treatment (from cycle one day one to the last day of cycle three). The severity of AEs will be graded according to the NCI-CTCAE version 5.0 A standard 3+3 dose escalation design will be used to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) while ensuring the safety and tolerability of the treatment. The study will test three dose levels of oxaliplatin. Dose Level 2 105 mg/m2 IP every 2 weeks Subjects will be accrued in cohorts of 3 to 6 subjects per dose level starting at Dose Level 0 (85 mg/m2). Escalation will continue until DLT stopping rules are met or the highest dose level is reached.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Subjects will be accrued in cohorts of 3 to 6 subjects per dose level starting at Dose Level 0 (85 mg/m2). Escalation will continue as described in the protocol until DLT stopping rules are met or the highest dose level is reached.
mFOLFIRI is a standardized chemotherapy regimen utilizing 5-fluorouracil, leucovorin, and irinotecan administered on day one of a 14-day cycle. 5-Fluorouracil, leucovorin, and irinotecan should be prepared and administered per the package insert and local institutional guidelines.
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Assess the maximum tolerated dose of intraperitoneal (IP) oxaliplatin with systemic IV 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) every 2 weeks in patients with unresectable peritoneal carcinomatosis of colorectal or appendiceal origin
The incidence of DLTs during the defined DLT period
Time frame: One Cycle is 14 days. The DLT evaluation period will be defined as the first three cycles of combination treatment (from cycle one day one to the last day of cycle three (42days)
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment and the IP catheter will be measured.
To assess the safety and feasibility of IP oxaliplatin when administered with systemic mFOLFIRI in patients with peritoneal carcinomatosis of colorectal or appendiceal origin.
Time frame: up to 3 years
The efficacy of IP oxaliplatin plus systemic mFOLFIRI in patients with peritoneal carcinomatosis of colorectal or appendiceal origin will be measured.
• Objective response rate (ORR) after four cycles of study therapy. ORR will be assessed by the number of patients obtaining a complete response plus the number of patients obtaining a partial response divided by the number of total response evaluable subjects.
Time frame: up to 3 years
The efficacy of IP oxaliplatin plus systemic mFOLFIRI in patients with peritoneal carcinomatosis of colorectal or appendiceal origin will be measured.
• Overall survival (OS) will be assessed as the time from trial initiation until death by any cause.
Time frame: Up to 3 years
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