Single Agent Regorafenib in Refractory Advanced Biliary Cancers

Exclusion Criteria

• •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
• •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 Participants permanently withdrawn from study participation will not be allowed to re-enter study.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