CPI-613 and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of CPI-613 (6,8-bis\[benzylthio\]octanoic acid), when used in combination with 5-FU (fluorouracil), in patients with non-resectable metastatic colorectal cancer who have failed FOLFOX (leucovorin calcium, fluorouracil and oxaliplatin), FOLFIRI (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) and, if Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type, then a epidermal growth factor receptor (EGFR) inhibitor-based regimen. SECONDARY OBJECTIVES: I. To assess the pharmacokinetic (PK), safety and efficacy of various doses of CPI-613, when used in combination with 5-FU, in patients with non-resectable metastatic colorectal cancer. OUTLINE: This is a dose-escalation study of 6,8-bis(benzylthio)octanoic acid. Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-4 and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 2 weeks for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 3 years.