Intraperitoneal Oxaliplatin and Fluorouracil for the Treatment of Patients With Peritoneal Metastases From Colorectal Cancer

PRIMARY OBJECTIVES: I. Determine safety, tolerability, and maximally tolerated dose (MTD) of intraperitoneal (IP) fluorouracil (5FU)+oxaliplatin. II. Determine pharmacokinetics (PK) of IP 5FU+oxaliplatin both in blood and peritoneal fluid. SECONDARY OBJECTIVES: I. Determine tumor-cell intrinsic effects, modulation of the tumor immune microenvironment, and changes in the makeup of circulating immune cells in response to IP 5FU+oxaliplatin. II. Identify preliminary response from IP 5FU+oxaliplatin: assess the rate of conversion from unresectable to resectable (determined by peritoneal carcinomatosis index \[PCI\] decreasing to \< 20) and response rates by imaging criteria. OUTLINE: This is a dose-escalation study of 5FU and oxaliplatin followed by a dose-expansion study. Patients undergo placement of indwelling IP port for chemotherapy infusion. Patients receive oxaliplatin and 5FU over 1-2 hours via IP infusion on days 1 and 15 of each cycle. Cycles repeat every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy, biopsy, computed tomography (CT)/magnetic resonance imaging (MRI), and collection of blood samples at screening and on study and undergo collection of IP fluid samples on study. After completion of study treatment, patients are followed up for 30 days. Patients with confirmed disease progression or who start a new anti-cancer therapy are followed up every 12 weeks until death, withdrawal of consent, or end of study.