Phase II Study Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
Background: Cholangiocarcinoma (CCA) is an aggressive cancer of the bile ducts. People with CCA have few treatment options and poor survival. Researchers want to see if a new drug can stop or slow CCA growth.
Objective: To find the safest and most effective dose of tivozanib to treat CCA and learn its overall response rate.
Eligibility: Adults ages 18 and older with CCA not removable with surgery and have been treated with at least one type of chemotherapy.
Design: Participants will be screened with the following: * Medical history * Physical exam * Assessment of their ability to do daily activities * Medicine review * Blood tests, including thyroid function tests * Urine tests * Electrocardiogram, to check heart function * Pregnancy test, if needed * Tumor biopsy, if needed * Computed tomography scans * Magnetic resonance imaging, if needed Some screening tests may be repeated during the study. Participants will be asked to enroll in protocol #13C0176. This will allow any remaining tumor or blood samples to be used in future research. Participants will take tivozanib by mouth, once a day for 21 days per cycle or every other day per cycle. Each cycle is 28 days. They can take the drug until they have bad side effects, their CCA gets worse, or if they become pregnant. They will record their blood pressure twice daily at home. They will also keep a medication diary of each dose of tivozanib they take and any side effects. Participants will have study visits before starting each new cycle and every 8 weeks. They will also have a follow-up visit 30 days after treatment ends at NIH, or if they are unable to come to NIH by phone, videocall, or other NIH-approved platform. Then they will be contacted 6 and 12 months later, and then once a year. ...
⁃ Participants with histologically or cytologically confirmed biliary tract cancer (BTC) (cholangiocarcinoma or gallbladder cancer). Archival tumor sample may be used but if archival tissue is not available or is not adequate, tissue biopsy will be required.
• Participants must have disease that is not amenable to resection.
• Participants must have had prior treatment with 1st line chemotherapy.
• Disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1.
• Age \>=18 years.
⁃ NOTE: Because no dosing or adverse event data are currently available on the use of tivozanib in participants \< 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• ECOG performance status \<= 2
• Adequate organ and marrow function as defined below:
∙ Hemoglobin \>= 8.0 g/dL
‣ Absolute Neutrophil Count \>= 1,000/mcL
‣ Platelets \>= 75,000/mcL
‣ Total Bilirubin \<= 2.5 X institutional upper limit of normal (ULN)
‣ AST(SGOT)/ALT(SGPT) \<= 5 X institutional ULN
‣ Creatinine Clearance \> 30
‣ Serum Albumin (g/L) \> 28
• Negative serum or urine pregnancy test at screening for individuals of childbearing potential (IOCBP), excepting identified false-positive pregnancy test results as permitted in the note below.
⁃ NOTE: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. IOCBP must have a negative pregnancy test (HCG blood or urine) during screening.
⁃ NOTE: Advanced biliary tract disease may secrete hormones that produce false-positive pregnancy test results. A false-positive result will be explicitly determined in this protocol at screening via a series of serial blood tests (i.e., serum HCG measurements) over a 5-day period (i.e., a minimum of a blood test on the first and fifth day of the 5-day period), in which a false-positive result not compatible with pregnancy will be defined as results indicating a consecutive, clinically low, constant level (i.e., no more than a 15% rate of increase) of HCG over the testing period. An ultrasound may be performed for clarification purposes as necessary.
• All participants (regardless of childbearing potential) must (all) agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 1 month after completion of treatment.
⁃ Ability of participant to understand and the willingness to sign a written informed consent document.
⁃ Ability and willingness to co-enroll on the tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors.