CholangiocarcinomaPhase 1/2NCT04645160
Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
A Phase 1/2 study testing Tivozanib in people with Cholangiocarcinoma and Bile Duct Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma, Bile Duct Neoplasm, Biliary Tract Malignancy
- What is being tested?
- Tivozanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2022to 31 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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".
Who cannot join
- 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.
- Previous malignant disease other than the target malignancy within the last 3 years with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, chronic lymphocytic leukemia, or thyroid carcinoma.
- Current active second primary malignancy, other than skin carcinoma (basal or squamous cell carcinoma), chronic lymphocytic leukemia not requiring active treatment, or differentiated thyroid carcinoma.
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- History of allergic reactions or known or suspected hypersensitivity attributed to compounds of similar chemical or biologic composition to tivozanib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy (see exceptions below), or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable and on suppressive therapy, if indicated. For participants with HBV infection who are currently on treatment, they are eligible if they have an undetectable HBV viral load.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Significant cardiovascular disease, including: Active clinically symptomatic left ventricular failure, uncontrolled hypertension, myocardial infarction, severe angina, or unstable angina within 3 months prior to administration of first dose of study drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring anti-arrhythmic medications.
- Uncontrolled hypertension, i.e., blood pressure (BP) of >= 150/90 mmHg; participants who have a history of hypertension controlled by medication must be on a stable dose of antihypertensive therapy such that there has been no increase in hypertensive medications or dosage (for at least -14 days) and meet all other inclusion criteria.
- Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders.
- GI Bleeding (e.g., esophageal varices or ulcer bleeding) within 3 months. (Note: For participants with a history of GI bleeding for more than 12 months or assessed as high risk for esophageal variceal by the Investigator, adequate endoscopic therapy according to institutional standards is required.)
- Complex biliary obstruction requiring bile duct stents at more than one level of the biliary tree or external biliary drainage.
- Recurrent episodes of cholangitis (>1) in the preceding 3 months prior to enrollment.
- Therapeutic anti-coagulation or anti-platelet therapy with the exception of low molecular weight heparin, aspirin, or factor Xa inhibitors.
- Pregnant or lactating individuals. Pregnant individuals are excluded from this study because based on findings in animals and its mechanism of action, tivozanib can cause fetal harm when administered to a pregnant individual. In animal reproduction studies, administration of tivozanib to pregnant rats caused adverse developmental outcomes including embryo- fetal mortality. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the individual with tivozanib, nursing (such as breastfeeding) should be discontinued if the individual is treated with tivozanib. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: 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.
Read more
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.
Read the detailed 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 driver in CCA cells and determined that this biology is driven by the interaction between XPO7 and a hitherto incompletely studied kinase, Ste-20 like kinase (SLK).
XPO7 binds to and promotes cytoplasmic localization and stabilization of SLK, which in turn activates oncogenic signaling. Targeting SLK expression via short hairpin RNA abrogates tumor formation in 3D culture and mice models, establishing SLK as a novel
target in biliary tract cancer.
The pan-vascular endothelial growth factor receptor (VEGFR) inhibitor tivozanib demonstrated activity against SLK in our in vitro screen, which we later confirmed with x-ray crystallography. Tivozanib abrogated growth of CCA tumorspheres, resulting in substantial tumor regression using murine xenograft models and patient-derived xenografts. Additionally, we evaluated tivozanib in our ex vivo tumor platform using a liver metastasis from a patient with XPO7-expressing biliary tract cancer and documented tumor cell apoptosis.
As reliable, molecular-targeted regimens either for first- or second-line therapy for the majority of patients with biliary tract cancer have remained elusive, these results support evaluation of tivozanib as a treatment option for patients with biliary tract cancer.
Objectives:
Determine the overall response rate (RECIST) of tivozanib in participants with biliary tract cancer (BTC) who were previously treated with first-line therapy.
Eligibility:
Participants with histologically or cytologically confirmed biliary tract cancer (BTC) not amenable to resection
Previous treatment with 1st line chemotherapy
Age >= 18 years of age
ECOG performance status of <=2
Preserved hepatic function
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase II study
Trial is a Simon minimax two-stage Phase II trial design to determine efficacy.
Treatment is in cycles of 28 days, 3 weeks on, 1 week off (with possible dose de-escalation if needed). Treatment evaluations for efficacy will be every 2 months (8 weeks).
Up to 21 participants may receive study intervention on this protocol
- Being tested
- Tivozanib
- Keywords
- CCA, FOTIVDA, pan-vascular endothelial growth factor receptor (VEGFR) inhibitor, XPO7, Ste-20 like kinase (SLK)
- Medical subject headings
- Cholangiocarcinoma, Bile Duct Neoplasms, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TivozanibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1/ Phase I | Experimental | Tivozanib, P.O. daily at 0.89 mg (given on Days 1-21 of every 28-day cycle) with intra-patient escalation to 1.34 mg daily (given on Days 1-21 of every 28-day cycle) and possible dose de-escalation to 0.89 mg every other day (without interruption for a 28-day cycle) if needed to determine RP2D Receives: Drug: Tivozanib |
| 2/ Phase II | Experimental | Tivozanib at the RP2D established in Phase I Receives: Drug: Tivozanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, every 8 weeks post-treatment
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.
Measured: Every 8 weeks (Phase I only)
Secondary outcomes (2)
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.
Measured: baseline, every 8 weeks post-treatment
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.
Measured: baseline, every 8 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2020
- Study start4 Mar 2022
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jonathan M Hernandez, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04645160
- Sponsor's protocol ID
- 210006
- Other IDs
- 21-C-0006
- Status last verified
- 13 Oct 2026
- First submitted
- 25 Nov 2020
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers
- ClinicalTrials.gov ID
- NCT04645160
- Acronym / sponsor ID
- 210006
- Keywords
- CCA, FOTIVDA, pan-vascular endothelial growth factor receptor (VEGFR) inhibitor, XPO7, Ste-20 like kinase (SLK)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 4 Mar 2022 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 27 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 driver in CCA cells and determined that this biology is driven by the interaction between XPO7 and a hitherto incompletely studied kinase, Ste-20 like kinase (SLK).
XPO7 binds to and promotes cytoplasmic localization and stabilization of SLK, which in turn activates oncogenic signaling. Targeting SLK expression via short hairpin RNA abrogates tumor formation in 3D culture and mice models, establishing SLK as a novel
target in biliary tract cancer.
The pan-vascular endothelial growth factor receptor (VEGFR) inhibitor tivozanib demonstrated activity against SLK in our in vitro screen, which we later confirmed with x-ray crystallography. Tivozanib abrogated growth of CCA tumorspheres, resulting in substantial tumor regression using murine xenograft models and patient-derived xenografts. Additionally, we evaluated tivozanib in our ex vivo tumor platform using a liver metastasis from a patient with XPO7-expressing biliary tract cancer and documented tumor cell apoptosis.
As reliable, molecular-targeted regimens either for first- or second-line therapy for the majority of patients with biliary tract cancer have remained elusive, these results support evaluation of tivozanib as a treatment option for patients with biliary tract cancer.
Objectives:
Determine the overall response rate (RECIST) of tivozanib in participants with biliary tract cancer (BTC) who were previously treated with first-line therapy.
Eligibility:
Participants with histologically or cytologically confirmed biliary tract cancer (BTC) not amenable to resection
Previous treatment with 1st line chemotherapy
Age >= 18 years of age
ECOG performance status of <=2
Preserved hepatic function
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase II study
Trial is a Simon minimax two-stage Phase II trial design to determine efficacy.
Treatment is in cycles of 28 days, 3 weeks on, 1 week off (with possible dose de-escalation if needed). Treatment evaluations for efficacy will be every 2 months (8 weeks).
Up to 21 participants may receive study intervention on this protocol
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/ Phase I | Experimental | Drug: TivozanibTivozanib, P.O. daily at 0.89 mg (given on Days 1-21 of every 28-day cycle) with intra-patient escalation to 1.34 mg daily (given on Days 1-21 of every 28-day cycle) and possible dose de-escalation to 0.89 mg every other day (without interruption for a 28-day cycle) if needed to determine RP2D |
| 2/ Phase II | Experimental | Drug: TivozanibTivozanib at the RP2D established in Phase I |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
- 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.
Key exclusion criteria (19 listed)
- 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.
- Previous malignant disease other than the target malignancy within the last 3 years with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, chronic lymphocytic leukemia, or thyroid carcinoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TivozanibOral 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. | Drug | 1/ Phase I, 2/ Phase II |
Primary outcome
Phase II: Determine the overall response rate by RECIST of tivozanib in patients with cholangiocarcinoma who were previously treated with first-line therapy.
Time frame: baseline, every 8 weeks post-treatment
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.
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.
Time frame: Every 8 weeks (Phase I only)
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.
2 secondary outcomes
Evaluate overall survival (OS) in patients with cholangiocarcinoma treated with tivozanib
Time frame: baseline, every 8 weeks post-treatment
Evaluate disease control response (DCR- complete response [CR] plus partial response [PR] plus stable disease [SD]) in patients with cholangiocarcinoma treated with tivozanib
Time frame: baseline, every 8 weeks post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan M Hernandez, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tivozanib in people with Cholangiocarcinoma and Bile Duct Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kathleen M Smith, R.N. ((240) 858-3531, kathleen.smith3@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase II: Determine the overall response rate by RECIST of tivozanib in patients with cholangiocarcinoma who were previously treated with first-line therapy. (time frame: baseline, every 8 weeks post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.