CPI-613 and Combination Chemotherapy in Treating Patients With Metastatic Pancreatic Cancer

Inclusion Criteria:

* Histologically and cytologically confirmed metastatic pancreatic adenocarcinoma
* Eastern Cooperative Oncology Group (ECOG) performance status being 0-1
* Expected survival \> 2 months
* 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 or hormonal therapy
* 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 oxalic 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 =\< 2.0 mg/dL or 177 µmol/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

Exclusion Criteria:

* Endocrine or acinar pancreatic carcinoma
* Previous radiotherapy for cerebral metastases, central nervous system (CNS) or epidural tumor
* Prior treatment with any chemotherapy for metastatic disease from pancreatic cancer
* Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 4 weeks prior to initiation of CPI-613 treatment
* 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)
* Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown)
* Lactating females
* Fertile men unwilling to practice contraceptive methods during the study period
* Life expectancy less than 2 months
* Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
* Unwilling or unable to follow protocol requirements
* Active 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
* Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment
* Requirement for immediate palliative treatment of any kind including surgery
* Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months
* Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient