Single Agent Regorafenib in Refractory Advanced Biliary Cancers

Inclusion criteria

• Histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease. Patients with ampullary carcinoma are not eligible.
• Have failed no more than 2 prior lines of systemic chemotherapy for advanced biliary cancer. Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible. If patient received adjuvant treatment and had disease recurrence after 6 months, they will only be eligible after failing one line of systemic chemotherapy used to treat the disease recurrence.
• Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1
• Measurable and non-measurable disease will be allowed.
• Must not have been treated with any vascular endothelial growth factor (VEGF) inhibitors. Prior 5-Fluorouracil (5-FU) or capecitabine treatment is allowed only if given as a radiosensitizer concurrently with radiation therapy at least 12 weeks prior to registration or if given as part of any adjuvant therapy regimen > 6 months prior to study enrollment.
• Life expectancy of at least 12 weeks (3 months)
• For patients who have received prior cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: 28 days have elapsed since that therapy (lesions that have not been treated with local therapy must be present and measureable.
• Able to understand and willing to sign the written informed consent form
• All acute toxic effects of any prior treatment have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
• Adequate bone marrow and liver function
• Participants can receive 5-FU or capecitabine.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug.
• Men and women of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug.
• Able to swallow and retain oral medication

Exclusion criteria

• Previous assignment to treatment during this study. Participants permanently withdrawn from study participation will not be allowed to re-enter study.
• Other investigational treatment during or within 21 days before starting study treatment
• Child Pugh B and C
• Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication
• Participants 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 informed consent
• Active malignancy except for nonmelanoma skin cancer or in situ cervical cancer. Potential participants surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before the trial are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form).
• Potential participants with phaeochromocytoma
• Potential participants with severe hepatic impairment (Child-Pugh Class C)
• 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 NCI-CTCAE v4.0
• 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
• Patients with seizure disorder requiring medication
• Persistent proteinuria >/= Grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hours, measured by urine protein:creatinine ratio on a random urine sample)
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
• Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.0 Grade 2 dyspnea)
• History of organ allograft (including corneal transplant)
• Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
• Any malabsorption condition
• Women who are pregnant or breast-feeding
• Any condition which, in the investigator's opinion, makes the potential participant unsuitable for trial participation
• Substance abuse, medical, psychological or social conditions that may interfere with participation in the study or evaluation of the study results