A Study to See the Effects That a New Combination of the Three Drugs, Nab-paclitaxel, Gemcitabine, and Cisplatin Has on Biliary Tract Cancer

Inclusion Criteria: 1. Histologically documented locally advanced or metastatic BTC (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) not previously treated with palliative systemic therapy or radiation 2. Unresectable disease based on the presence of clinically and/or radiologically documented measurable disease based on RECIST 1.1. Patients must have measurable disease; evaluable only disease will not be permitted. 3. ECOG performance status of 0 - 1. 4. Age ≥ 18 years. 5. Life expectancy of at least 3 months based on discretion of treating oncologist. 6. Adequate hematologic function defined by the following laboratory parameters: * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100 x 109/L * Absolute granulocyte count ≥ 1.5 x 109/L 7. Adequate hepatic and renal function defined by the following laboratory parameters: * AST and ALT and alkaline phosphatase ≤ 2.5 X upper limit of institutional normal (≤ 5 if liver metastases) * bilirubin ≤ 1.5 X upper limit of institutional normal * serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault formula 8. Patients may have received prior surgery if this surgery was ≥ 4 weeks before study entry and patients must have recovered from the toxic effects of this treatment. 9. Prothrombin time- international normalized ratio (PT-INR) and partial thromboplastin time (PTT) must be within +/- 15% normal range. 10. Patients who have treated brain metastasis (via local radiation standards or surgical resection or local ablative techniques) and who are either off steroids or on a stable dose of steroids for at least one month (30 days), AND who are off anticonvulsants, AND have radiological documented stability of lesions for at least 3 months may be eligible. Each case should be discussed with the study Chair. 11. Patients must have the ability to read, understand, and sign an informed consent and must be willing to comply with study treatment and follow-up. 12. Female subjects of childbearing potential, defined as a sexually mature woman who 1) has not undergone hysterectomy or bilateral oophorectomy OR 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time during the preceding 24 consecutive months) must: * either commit to true abstinence or agree to the use of a 2 physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive with spermicide; or vasectomized partner) while on clinical trial and for at least 3 months following the last does of study medication; and * has a negative serum pregnancy test (β-hCG) result at screening. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 6 months following study medication discontinuation, even if he has undergone a success vasectomy. Exclusion Criteria: 1. Patients who have received prior palliative chemotherapy for their advanced BTC. 2. Prior curative or palliative radiation treatment to the pelvis or radiation therapy to ≥ 25% of bone marrow stores. 3. History of bowel obstruction due to peritoneal metastases or clinically documented ascites requiring paracenteses. 4. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment, unless at least 5 years have elapsed since last treatment and the patient is considered cured). 5. Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment. 6. Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications. 7. Any serious medical condition within 6 months prior to study entry such as myocardial infarction, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases, uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder, serious infection, active peptic ulcer disease, or other medical condition that may be aggravated by treatment. 8. Pre-existing neuropathy ≥ grade 1 from any cause. 9. Patients with unstable metastasis to the central nervous system (CNS). A CT scan or MRI is NOT required to rule out brain metastases unless there is clinical suspicion of CNS involvement. 10. Pregnant or lactating women; women of child bearing potential must have a negative serum pregnancy test within 7 days of trial registration. Women or men of child bearing potential must use effective contraception (defined by the treating physician) which must be documented in study CRFs. 11. History of allergic reaction to planned study medications. 12. Patient has a ≥ 20% decrease in serum albumin level between baseline visit, if available, and within 72 hours prior to first study treatment dose. 13. Patient is on coumadin. 14. History of interstitial lung disease. 15. History of connective tissue disorders (e.g. lupus, scleroderma, polyarteritis nodosa). 16. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures. 17. Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study, places the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study.