Ignite Creation Date:
2024-05-06 @ 2:03 AM
Last Modification Date:
2024-10-26 @ 11:13 AM
Study NCT ID:
NCT01967576
Status:
COMPLETED
Last Update Posted:
2021-01-06
First Post:
2013-10-19
Brief Title:
Phase II Study of Axitinib AG-013736 With Evaluation of the VEGF-pathway in Metastatic Recurrent or Primary Unresectable PheochromocytomaParaganglioma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study of Axitinib AG-013736 With Evaluation of the VEGF-pathway in Metastatic Recurrent or Primary Unresectable PheochromocytomaParaganglioma
Status:
COMPLETED
Status Verified Date:
2020-12
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
Most treatments for malignant pheochromocytomasparagangliomas PHEOPGL are palliative and multidisciplinary Chemotherapy using the combination of cyclophosphamide vincristine and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO with more than 50 complete or partial tumor response and more than 70 complete or partial biochemical response
Vascular endothelial growth factor VEGF expression and evidence of angiogenesis has been found in many PHEOPGL so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEOPGL
Axitinib AG-013736 is an oral potent and selective inhibitor of vascular endothelial growth factor VEGF receptors 1 2 and 3 Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued
Given the known clinical safety and efficacy of axitinib an assessment of its activity in PHEOPGL and its impact on the VEGF pathway in PHEOPGL could provide valuable information
Objectives
Determine the response rate of metastatic PHEOPGL to axitinib AG-013736
Determine the progression-free survival of metastatic PHEOPGL treated with axitinib AG-013736
Explore the relationship of potential biological markers of axitinib activity with clinical outcomes
Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid DNA examination
Eligibility
Adults with a confirmed pathologic diagnosis of PHEOPGL by the Laboratory of Pathology National Cancer Institute NCI
Biochemical evidence of PHEOPGL
Imaging confirmation of metastatic locally advanced or unresectable disease
Measurable disease at presentation
Eastern Cooperative Oncology Group ECOG performance status less than or equal to 2
Patients must not have received prior therapy with a tyrosine kinase TK inhibitor
Design
Phase II open label non-randomized trial
Patients with metastatic pheochromocytomaparaganglioma will receive axitinib AG-013736 twice a day BID in eight-week cycles
Patients will be evaluated for response every eight weeks using Response Evaluation Criteria in Solid Tumors RECIST criteria
Tumor biopsies are not mandatory but every attempt will be made to obtain these from patients prior to starting axitinib and again 20 - 30 days after treatment has begun
Approximately 12 to 37 patients will be needed to achieve the objectives of the trial
Most treatments for malignant pheochromocytomasparagangliomas PHEOPGL are palliative and multidisciplinary Chemotherapy using the combination of cyclophosphamide vincristine and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO with more than 50 complete or partial tumor response and more than 70 complete or partial biochemical response
Vascular endothelial growth factor VEGF expression and evidence of angiogenesis has been found in many PHEOPGL so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEOPGL
Axitinib AG-013736 is an oral potent and selective inhibitor of vascular endothelial growth factor VEGF receptors 1 2 and 3 Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued
Given the known clinical safety and efficacy of axitinib an assessment of its activity in PHEOPGL and its impact on the VEGF pathway in PHEOPGL could provide valuable information
Objectives
Determine the response rate of metastatic PHEOPGL to axitinib AG-013736
Determine the progression-free survival of metastatic PHEOPGL treated with axitinib AG-013736
Explore the relationship of potential biological markers of axitinib activity with clinical outcomes
Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid DNA examination
Eligibility
Adults with a confirmed pathologic diagnosis of PHEOPGL by the Laboratory of Pathology National Cancer Institute NCI
Biochemical evidence of PHEOPGL
Imaging confirmation of metastatic locally advanced or unresectable disease
Measurable disease at presentation
Eastern Cooperative Oncology Group ECOG performance status less than or equal to 2
Patients must not have received prior therapy with a tyrosine kinase TK inhibitor
Design
Phase II open label non-randomized trial
Patients with metastatic pheochromocytomaparaganglioma will receive axitinib AG-013736 twice a day BID in eight-week cycles
Patients will be evaluated for response every eight weeks using Response Evaluation Criteria in Solid Tumors RECIST criteria
Tumor biopsies are not mandatory but every attempt will be made to obtain these from patients prior to starting axitinib and again 20 - 30 days after treatment has begun
Approximately 12 to 37 patients will be needed to achieve the objectives of the trial
Detailed Description:
Background
Most treatments for malignant pheochromocytomasparagangliomas PHEOPGL are palliative and multidisciplinary Chemotherapy using the combination of cyclophosphamide vincristine and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO with more than 50 complete or partial tumor response and more than 70 complete or partial biochemical response
Vascular endothelial growth factor VEGF expression and evidence of angiogenesis has been found in many PHEOPGL so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEOPGL
Axitinib AG-013736 is an oral potent and selective inhibitor of vascular endothelial growth factor VEGF receptors 1 2 and 3 Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued
Given the known clinical safety and efficacy of axitinib an assessment of its activity in PHEOPGL and its impact on the VEGF pathway in PHEOPGL could provide valuable information
Objectives
Determine the response rate of metastatic PHEOPGL to axitinib AG-013736
Determine the progression-free survival of metastatic PHEOPGL treated with axitinib AG-013736
Explore the relationship of potential biological markers of axitinib activity with clinical outcomes
Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid DNA examination
Eligibility
Adults with a confirmed pathologic diagnosis of PHEOPGL by the Laboratory of Pathology National Cancer Institute NCI
Biochemical evidence of PHEOPGL
Imaging confirmation of metastatic locally advanced or unresectable disease
Measurable disease at presentation
Eastern Cooperative Oncology Group ECOG performance status less than or equal to 2
Patients must not have received prior therapy with a tyrosine kinase TK inhibitor
Design
Phase II open label non-randomized trial
Patients with metastatic pheochromocytomaparaganglioma will receive axitinib AG-013736 twice a day BID in eight-week cycles
Patients will be evaluated for response every twelve weeks - 1 week using Response Evaluation Criteria in Solid Tumors RECIST criteria
Approximately 12 to 37 patients will be needed to achieve the objectives of the trial
Most treatments for malignant pheochromocytomasparagangliomas PHEOPGL are palliative and multidisciplinary Chemotherapy using the combination of cyclophosphamide vincristine and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO with more than 50 complete or partial tumor response and more than 70 complete or partial biochemical response
Vascular endothelial growth factor VEGF expression and evidence of angiogenesis has been found in many PHEOPGL so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEOPGL
Axitinib AG-013736 is an oral potent and selective inhibitor of vascular endothelial growth factor VEGF receptors 1 2 and 3 Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued
Given the known clinical safety and efficacy of axitinib an assessment of its activity in PHEOPGL and its impact on the VEGF pathway in PHEOPGL could provide valuable information
Objectives
Determine the response rate of metastatic PHEOPGL to axitinib AG-013736
Determine the progression-free survival of metastatic PHEOPGL treated with axitinib AG-013736
Explore the relationship of potential biological markers of axitinib activity with clinical outcomes
Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid DNA examination
Eligibility
Adults with a confirmed pathologic diagnosis of PHEOPGL by the Laboratory of Pathology National Cancer Institute NCI
Biochemical evidence of PHEOPGL
Imaging confirmation of metastatic locally advanced or unresectable disease
Measurable disease at presentation
Eastern Cooperative Oncology Group ECOG performance status less than or equal to 2
Patients must not have received prior therapy with a tyrosine kinase TK inhibitor
Design
Phase II open label non-randomized trial
Patients with metastatic pheochromocytomaparaganglioma will receive axitinib AG-013736 twice a day BID in eight-week cycles
Patients will be evaluated for response every twelve weeks - 1 week using Response Evaluation Criteria in Solid Tumors RECIST criteria
Approximately 12 to 37 patients will be needed to achieve the objectives of the trial
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 |
|---|---|---|---|
| 14-C-0001 | None | None | None |