Phase 2 Study of the Anti-Angiogenesis Agent Axitinib (AG-013736) in Patients With Stage III Malignant Melanoma
The American Cancer Society estimates that there will be about 68,720 new cases of melanoma
(29,900 in men and 25,200 in women) annually in the United States, and about 8,650 people
will die from this cancer. The systemic therapy of advanced disease remains palliative
until new agents are found that might improve the survival of patients with stage III
melanoma. However, because large-scale clinical trials are often necessary to demonstrate
the safety and effectiveness of a drug, it is desirable to determine if new agents provide
some measure of effectiveness of these new agents prior to investing in such studies.
Melanomas are often vascular, and a decrease in the number of blood vessels that supply the
tumor may starve it of needed nutrients. An approach to blocking the growth of blood
vessels that supply the tumor is to inhibit the vascular endothelial growth factor receptor
tyrosine kinase (VEGFR TK) signaling pathway. Axitinib (AG 013736) is a VEGFR TK inhibitor.
Besides having the potential to block the growth of blood vessels (angiogenesis) through
VEGFR TK inhibition, Axitinib also has the additional antitumor potential through platelet
derived growth factor receptor (PDGFR) TK inhibition.
Because of the poor prognosis of patients with stage III melanoma and indications that
anti-angiogenesis compounds might have clinically meaningful activity in this disease, a
Phase 2 trial of the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK)
inhibitor Axitinib (AG 013736) is warranted to determine its activity and tolerability for
Stage III melanoma. As a Phase 2 open label study of Axitinib, each consented patient who
meets all inclusion criteria will initially receive 5 mg orally twice daily. Study tests,
procedures and monitoring will be performed throughout the study to determine therapy
response rate and patient safety.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine progression-free survival (PFS)
The primary objective of this study is to determine the activity of AG-013736 in metastatic melanoma as measured by the overall response rate, complete response (CR) and partial response (PR) by RECIST. A response will also be considered to have occurred if there is a >/= 30% reduction in the involved nodal basin specific uptake value (SUV) on PET/CT.
John P. Fruehauf, MD, PhD
Chao Family Comprehensive Cancer Center
United States: Food and Drug Administration
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