NCT03839498

Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary Objective: To determine the response rate (RR) of metastatic or locally advanced pheochromocytoma/paraganglioma to axitinib administered daily. Secondary Objectives: * Determine the progression-free survival. * In an exploratory manner examine the extent of activation of the VEGFR pathway in pheochromocytoma/paraganglioma using a semi-quantitative immunohistochemistry assay and examine the relationship with response to therapy. * Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination.

Detailed description

The long-term survival for malignant pheochromocytoma/paraganglioma (PHEO/PGL) may be limited because of its hormonal effects as well as its aggressive behavior and dissemination, particularly in some hereditary PHEO/PGL. Although several therapeutic modalities have been used to palliate malignant PHEO/PGL, a continued search for new agents to address the malignancy is needed to improve outcomes. One approach is to utilize drugs that target signaling pathways leading to decreased proliferation and survival of cancer cells. Some data in the literature suggests that in malignant PHEO/PGL, VEGF seems to play a role in the biology of the cancer and thus, its inhibition could reduce tumor growth. Sunitinib and imatinib has been used in a limited number of malignant pheochromocytomas with varying responses. Axitinib was designed to inhibit VEGFR that participates in tumor angiogenesis. In order to determine the activity of axitinib in tumor and hormonal responses in malignant PHEO/PGL, it will be used as a single agent in this study. The combination of cyclophosphamide; vincristine and dacarbazine have been shown to produce partial responses in malignant PHEO/PGL. The majority of the patients may have already received this combination or will receive this combination chemotherapy in the future. The goal is to develop multiple lines of effective treatments for this disease.

Conditions

• Pheochromocytoma
• Paraganglioma

Interventions

Type	Name	Description
DRUG	Axitinib	Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Starting dose level 1: 5 mg every morning; 5 mg every evening. Dose level 2: 7 mg every morning; 7 mg every evening. Dose level 3: 10 mg every morning; 10 mg every evening. Dose level -1: 3 mg every morning; 3 every evening. Dose level -2: 2 mg every morning; 2 mg every evening. Axitinib is supplied as 1 and 5-mg tablets and is administered orally twice a day with or without food, each morning and evening (i.e., every 12 hours). Axitinib will be given as self-administered.

Timeline

• Start date: 2019-01-22
• Primary completion: 2027-01-01
• Completion: 2027-02-01
• First posted: 2019-02-15
• Last updated: 2026-03-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study