Clinical Trials

Inclusion Criteria:

• Presence of an unresectable hepatobiliary mass or metastatic disease (consistent with cholangiocarcinoma, as evidenced by histology or cytology (augmented by fluorescence in situ hybridization (FISH) where appropriate), for which treatment with gemcitabine plus cisplatin is intended. Intrahepatic and extrahepatic cholangiocarcinoma patients may be enrolled.
• For patients enrolled in the Dose Escalation Phase, one or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST v. 1.1 (e.g., malignant ascites). All patients enrolled to the Randomized Study Phase must have measurable disease only.
• Laboratory data as specified below:
  • Hematology: Absolute neutrophil count (ANC) >1,500 cells/mm3, platelet count >100,000 cells/ mm.cu. and hemoglobin > 9 g/dL;
  • Hepatic: bilirubin <1.5 X Upper Limit of Normal (ULN); alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN;
  • Renal: serum creatinine within normal limits (WNL), defined as within 25% of the institution's stated reference range, or a calculated creatinine clearance >45 mL/min/1.73 m. sq. for patients with abnormal, increased, creatinine levels;
  • Coagulation: International Normalized Ratio (INR) < 1.5 times normal, activated Partial Thromboplastin Time (aPTT) < 1.5 times normal. Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible for the trial if INR and aPTT are within the acceptable therapeutic limits for the institution.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1.
• Presence of an (ECOG) Performance Status 0 - 1.

Exclusion Criteria:

• A history of prior systemic treatment with gemcitabine or cisplatin. At least six months must have elapsed if gemcitabine or cisplatin was administered in an adjuvant treatment setting. Patients enrolled in the Expansion Cohort, Exploratory Cohorts, and the Randomized Phase must not have received prior systemic chemotherapies, including chemoradiation therapy for cholangiocarcinoma.
• Seizure disorders requiring anticonvulsant therapy.
• Known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
• Major surgery other than diagnostic surgery, within 4 weeks prior to the first dose of test drug, minor surgery including diagnostic surgery within 2 weeks (14 days) excluding central IV port placements and needle aspirate/core biopsies. Radio frequency ablation or transcatheter arterial chemoembolization within 6 weeks prior to the first dose of test drug.
• Treatment with radiation therapy or surgery within one month prior to study entry.
• Treatment with chemotherapy or investigational drugs within 21 days prior to the screening visit. Acute toxicities from prior therapy must have resolved to Grade ≤ 1 above baseline.
• Patients with a history of another malignancy within 3 years of the baseline visit. (Patients with cutaneous carcinomas or in-situ carcinomas will be considered for study entry on a case-by-case basis).
• Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure).
• Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis which would not permit the patient to be managed according to the protocol.
• Difficulty with swallowing or an active malabsorption syndrome.
• Chronic diarrhea (excess of 2-3 stools/day above normal frequency).
• Gastrointestinal diseases including ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• History of gastric or small bowel surgery involving any extent of gastric or small bowel resection.
• Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.