NCT01967576

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

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

Detailed 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

Conditions

• Pheochromocytoma
• Paraganglioma

Interventions

Type	Name	Description
DRUG	Axitinib (AG-013736)	5 mg twice a day on a 28-day cycle.

Timeline

• Start date: 2013-10-19
• Primary completion: 2015-06-29
• Completion: 2020-12-01
• First posted: 2013-10-23
• Last updated: 2021-01-06
• Results posted: 2020-08-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study