Clinical Trial: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
Brief Summary:
Background:
- Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) 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.
- VEGF expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.
- 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 PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.
Objectives:
- Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).
- Determine the progression-free survival of metastatic PHEO/PGL 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 DNA examination.
Background:
- Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) 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.
- VEGF expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.
- 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 PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.
Objectives:
- Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).
- Determine the progression-free survival of metastatic PHEO/PGL 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 DNA examination.
Original Secondary Outcome:
- Determine the progression- free survival. [ Time Frame: 4 years ]
- Pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination [ Time Frame: 4 years ]
- Explore the relationship of potential biological markers of axitinib activity with clinical outcomes. [ Time Frame: 4 years ]
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: October 19, 2013
Date Started: October 15, 2013
Date Completion: October 1, 2017
Last Updated: May 12, 2017
Last Verified: March 31, 2017