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

Inclusion Criteria:

Histologically and cytologically confirmed metastatic colorectal adenocarcinoma (colon, rectal or colorectal cancer) that is not resectable
Have failed or have not tolerated FOLFOX, FOLFIRI and, if KRAS wild type, then a EGFR inhibitor-based regimen
Eastern Cooperative Oncology Group (ECOG) performance status being 0-2
Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
At least 2 weeks must have elapsed from any prior surgery
Granulocyte count >= 1500/mm^3
White blood cell (WBC) >= 3500 cells/mm^3 or >= 3.5 bil/L
Platelet count >= 100,000 cells/mm^3 or >= 100 bil/L
Absolute neutrophil count (ANC) >= 1500 cells/mm^3 or >= 1.5 bil/L
Hemoglobin >= 9 g/dL or >= 90 g/L
Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 5 x UNL if liver metastases present)
Bilirubin =< 1.5 x UNL
Serum creatinine =< 1.5 mg/dL or 13 umol/L
International normalized ratio or INR must be =< 1.5 unless on therapeutic blood thinners
No evidence of active infection and no serious infection within the past month
Mentally competent, ability to understand and willingness to sign the informed consent form
At least one measurable lesion as assessed by computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria

Exclusion Criteria:

Therapy with CPI-613 prior to participating in this trial
Known hypersensitivity to 5-FU injection, poor nutritional state, known dipyrimidine dehydrogenase deficiency, or taking sorivudine (such as Usevir, brovavir, etc.)
History of hypersensitivity to active or inactive excipients of any component of treatment
Previous radiotherapy for central nervous system metastases
Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of treatment with study drugs
Serious medical illness that would potentially increase patients' risk for toxicity
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
History of abdominal fistula or gastrointestinal perforation =< 6 months prior to treatment with study drugs
Pregnant women, or women of child-bearing potential not using reliable means of contraception
Lactating females
Fertile men unwilling to practice contraceptive methods during the study period
Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
Unwilling or unable to follow protocol requirements
Symptomatic heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failure
Patients with a history of myocardial infarction that is < 3 months prior to registration
Evidence of active infection, or serious infection within the past month
Patients with known human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment; steroid use for management of refractory pain or for contrast induced allergy is allowed
Requirement for immediate palliative treatment of any kind including surgery
Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient