Regorafenib in Treating Patients with Advanced or Metastatic Biliary Tract Cancer Who Failed First-Line Chemotherapy

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of biliary tract adenocarcinoma/ cholangiocarcinoma (including primary intra- and extrahepatic diseases); pathologic confirmation may be made from the primary or a metastatic site
• Must have locally advanced or distant metastatic disease that is not surgically curable
• Failed first-line chemotherapy (including systemic and local-regional therapy)
• Life expectancy >= 12 weeks (3 months)
• Performance status Eastern Cooperative Oncology Group (ECOG) =< 1
• Total bilirubin =< 3.0 x the upper limits of normal (ULN) (biliary stenting or percutaneous biliary drainage are allowed for cancer related biliary obstruction)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5.0 x ULN
• Alkaline phosphatase limit =< 2.5 x ULN (=< 5.0 x ULN for subjects with intrahepatic involvement of their cancer)
• Serum creatinine =< 1.5 x the ULN
• International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN; (patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care)
• Platelet count >= 75,000 /mm^3
• Hemoglobin (Hb) >= 9 g/dL
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Blood transfusion to meet the inclusion criteria will not be allowed
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Patients (men and women) of childbearing potential must agree to use double barrier method of birth control beginning at the signing of the informed consent form (ICF) until at least 3 months after the last dose of study drug
• Patients must be able to swallow and retain oral medication
• Patients must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure

Exclusion Criteria

• Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
• Uncontrolled hypertension (systolic pressure >= 140 mm Hg or diastolic pressure >= 90 mm Hg on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including: * Congestive heart failure – New York Heart Association (NYHA) > class II * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Unstable angina (angina symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event >= grade 3 within 4 weeks prior to prior to registration
• Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of the study registration
• Previous exposure to vascular endothelial growth factor (VEGF) inhibitor(s)
• Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology from biliary tract cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years prior to registration are allowed; all cancer treatments must be completed at least 3 years prior to prior to registration)
• Patients with pheochromocytoma
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection > grade 2
• Symptomatic metastatic brain or meningeal tumors
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• Renal failure requiring hemo-or peritoneal dialysis
• Dehydration grade >= 1
• Patients with seizure disorder requiring medication
• Proteinuria >= grade 3 (> 3.5 g/24 hours, measured by urine protein: creatinine ratio on a random urine sample)
• Active signs and symptoms of interstitial lung disease pleural effusion or ascites that causes respiratory compromise (>= grade 2 dyspnea)
• History of organ allograft (including corneal transplant)
• Known or suspected allergy or hypersensitivity to any of the study drug classes
• Any malabsorption condition
• Women who are pregnant or breast-feeding
• Any condition which, in the investigator’s opinion, makes the subject unsuitable for trial participation
• Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment regorafenib; however, the palliative radiation therapy (XRT) to non-targeted lesions is allowed
• Prior use of regorafenib
• Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 28 days prior to registration
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (biliary stenting or percutaneous biliary drainage are not included)
• Use of any herbal remedy (e.g. St. John’s wort [Hypericum perforatum])