Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma

Pheochromocytoma Clinical Trial

Official title: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma

Status Completed

Clinical Trial 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.

• Vascular endothelial growth factor (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 deoxyribonucleic acid (DNA) examination.

Eligibility:

• Adults with a confirmed pathologic diagnosis of PHEO/PGL by the Laboratory of Pathology, National Cancer Institute (NCI)

• Biochemical evidence of PHEO/PGL

• 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 pheochromocytoma/paraganglioma 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

Clinical Trial Description

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.

• Vascular endothelial growth factor (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 deoxyribonucleic acid (DNA) examination.

Eligibility:

• Adults with a confirmed pathologic diagnosis of PHEO/PGL by the Laboratory of Pathology, National Cancer Institute (NCI)

• Biochemical evidence of PHEO/PGL

• 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 pheochromocytoma/paraganglioma 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 ;

Related Conditions & MeSH terms

• Paraganglioma
• Pheochromocytoma

• NCT number: NCT01967576
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: October 19, 2013
• Completion date: December 1, 2020