Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Chemotherapy, small molecule or radiation therapy within 2 weeks prior to administration of first dose of study drug.
Prior treatment with Tivozanib.
History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (e.g., no lactulose, rifaximin, etc. if used for purposes of hepatic encephalopathy).
Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
Trial design
Design model
Sequential
Treatments tested in this trial
Tivozanib
DrugOral 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.
Treatment groups
31 Participants
are divided into 2 treatment groupsGroup A: 1/ Phase IExperimental treatment 1 intervention
Group B: 2/ Phase IIExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase II: Determine the overall response rate by RECIST of tivozanib in patients with cholangiocarcinoma who were previously treated with first-line therapy.
Patients will be re-evaluated for response every 8 weeks after start of treatment. The Phase II clinical response rate (CR+PR) will be determined and reported along with a 95% confidence interval.
Time frame
baseline, every 8 weeks post-treatment2
Phase I: Determine safety and establish the recommended Phase II dose (RP2D) of tivozanib in patients with cholangiocarcinoma who were previously treated with first-line chemotherapy.
List of adverse event frequency and grade. Patient DLTs will be counted and reported to determine the safety and tolerability of tivozanib and to establish the recommended Phase II dose (RP2D) using a standard 3+3 design.
Time frame
Every 8 weeks (Phase I only)Secondary outcomes
1
Evaluate overall survival (OS) in patients with cholangiocarcinoma treated with tivozanib
CT or MRI will be used for response criteria. PFS and OS will be determined using Kaplan-Meier estimates.
Time frame
baseline, every 8 weeks post-treatment2
Evaluate disease control response (DCR- complete response [CR] plus partial response [PR] plus stable disease [SD]) in patients with cholangiocarcinoma treated with tivozanib
CT or MRI will be used for response criteria. DCR (CR plus PR plus SD) will be determined and reported along with 95% confidence intervals. Wherever possible, duration of DCR will be reported.
Time frame
baseline, every 8 weeks post-treatmentSponsors and contacts
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Source ClinicalTrials.gov