Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04)

Inclusion: * Patients must have a pathologically or cytologically confirmed carcinoma (except neuroendocrine) of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gallbladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded. * Patients may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC. Prior peri-operative chemotherapy is permitted provided it was completed \> 6 months from enrollment. * Patients may have received prior radiation, chemoembolization, radioembolization or other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity. Extrahepatic palliative radiation is permitted if completed ≥ 2 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity * Patients must have radiographically measurable disease (as per RECISTv1.1) in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site. * Must be ≥ 18 years of age. * Must have an ECOG performance status of 0-1. * Ability to understand and willingness to sign IRB-approved informed consent. * Willing to provide archived tissue, if available, from a previous diagnostic biopsy or surgery. * Must be able to tolerate CT and/or MRI with contrast. * Adequate organ function (per protocol) obtained ≤ 2 weeks prior to enrollment. * Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation and for 6 months (for men and women) following completion of study therapy. Exclusions: * Prior history of brain metastasis (unless previously treated, asymptomatic and stable for at least 3 months) or organ transplant. * Underwent a major surgical procedure \< 4 weeks prior to enrollment. * Active second malignancy other than in situ cancer or localized prostate cancer (Gleason score \<8). Patients with history of other malignancy are eligible provided primary treatment of that cancer was completed \> 1 year prior to enrollment and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy. * Ongoing active, uncontrolled infection (must be afebrile for \> 48 hours off antibiotics) . * Psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements. * Pregnancy or breastfeeding. (Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child. All females of childbearing potential \[not surgically sterilized and between menarche and 1 year post menopause\] must have a negative screening pregnancy test.) * Active heart disease including symptomatic heart failure (NYHA class 3 or 4), unstable angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease. * Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness would be excluded. * Prolonged QTcF interval \>480 msec. * Known hypersensitivity to cisplatin, gemcitabine or CPI-613, or its inactive components.