Phase II Study Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
National Cancer Institute (NCI)
Summary
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.
Description
Background: Biliary Tract Cancers (BTC) (cholangiocarcinoma (CCA) and gallbladder cancer (GBC)) are aggressive malignancies that remain a clinical challenge with limited treatment options and poor survival. Combination chemotherapy with gemcitabine and cisplatin is the most validated first-line treatment, but the response rate approaches only 22% and median progression free survival is 8 months. Cytoplasmic accumulation of the nuclear export protein exportin 7, XPO7, portends poor outcomes for patients with biliary tract cancer. Using pre-clinical models, we established XPO7 as an oncogenic…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: 1. 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. 2. Participants must have disease that is not amenable to resection. 3. Participants must have had prior treatment with 1st line chemotherapy. 4. Disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1. 5. Age \>=18 years. NOTE: Because no dosing or ad…
Interventions
- DrugTivozanib
Oral tivozanib taken daily for Days 1-21 continuously (of each 28-day cycle) followed with 7 days off medication (except for patients in DL-1, with dosing every other day of the 28-day cycle). Phase I: The starting dose (DL1) is 0.89 mg taken once a day continuously for Days 1-21 with 1 week off medication (except for those patients assigned to DL-1, where tivozanib should be taken every other day, around 48 hours apart in 28-day cycle). Patients may escalate to 1.34 mg taken once a day (DL2) continuously for Days 1-21 with 1 week off medication for their second cycle if there are no dose-limiting toxicities. Phase II: Tivozanib dose level will be at the recommended Phase II dose (RP2D) established in Phase I.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland