Ignite Creation Date:
2024-05-06 @ 3:28 PM
Last Modification Date:
2024-10-26 @ 1:50 PM
Study NCT ID:
NCT04645160
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2020-11-25
Brief Title:
Evaluating Efficacy of Tivozanib AV-951 in Biliary Tract Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study Evaluating Efficacy of Tivozanib AV-951 in Biliary Tract Cancers
Status:
RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 21-C-0006 | None | None | None |