Study of Regorafenib for Urothelial Cancer Following Chemotherapy (UAB 1477)

Inclusion Criteria

• Patients must have pathologically or cytologically proven transitional cell carcinoma of the urothelium.
• Progressive disease after 1-3 prior chemotherapy regimens (perioperative chemotherapy within 12 months will be considered one regimen).
• Prior regimen must be within 6 months of registration
• Measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
• Patients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable (T4b) transitional cell carcinoma.
• Age ≥19 years
• Life expectancy of at least 12 weeks (3 months)
• Subjects must be able to understand and be willing to sign the written informed consent form.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
• Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Serum creatinine ≤ 1.5 x the ULN
• International normalized ratio (INR) less than or equal to 1.5 x ULN. (Subjects who are prophylactically 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 >100, 000/mm3, hemoglobin (Hb) >8 g/dL, absolute neutrophil count (ANC) 1500/mm3. The patient cannot be transfused in order to meet study entry criteria.
• 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. The definition of adequate contraception will be based on the judgment of the investigator.
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form until at least 3 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
• Subject must be able to swallow and retain oral medication.

Exclusion Criteria

• Component of small-cell cancer or sarcomatoid cancer
• Prior therapy with any systemic therapy (chemotherapy or biologic therapy) within twenty-eight days prior to study entry
• Patients must have recovered from toxicities from prior systemic anticancer treatment or local therapies.
• Patients who have undergone major surgery 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 ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
• Subjects 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 start of study treatment within 6 months of informed consent.
• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histo