A Phase II, Open Label, Uncontrolled and Multicenter Trial of Pazopanib Given as a Single Agent in Patients With Progressive Advanced/Metastatic Neuroendocrine Tumors (NET): a Search for Activity, Safety, and Predictive Biomarkers

Detailed Summary

The incidence of new diagnosed patients with NET of the digestive tract including carcinoid and pancreatic islet cells tumors ranges from 2 to 10 per 100,000 in the western Countries (Kulke M, Mayer R. N Engl J Med 340:858-868, 1999). Despite of the low incidence, the prevalence of these tumors is high because of their relatively long survival estimated in 35% at 5 years for those patients with well or moderate differentiated tumors (Yao JC, et al. J Clin Oncol. 2008;26:3063-3072). In fact, digestive NETs are the second most prevalent tumors derived from the digestive tract after colorectal carcinoma. NETs are characterized by abundant vasculature, moreover VEGFR and VEGFR are overexpressed in 60-84% of the carcinoids and pancreatic islet cells NETs (Zhang et al. Cancer 2007;109:1478-1486). Other pro-angiogenic factors like the platelet derived growth factor (PDGFR) have been also involved in NET progression and development (Chaudhry A, et al.Cancer Res 1992;52:1006-12). Pazopanib is an oral tyrosine kinase inhibitor of the VEGFR, PDGFR and KIT with a dual activity both as an antiangiogenic and also and anti-tumoral agent (Kumar et al. Mol Cancer Ther2007;6:2012-2021, Hurwitz et al. Clin Cancer Res 2009;15:4220-4227). Pazopanib seems to have a better toxicity profile versus the other antiangiogenic tyrosine kinase inhibitors and has already shown activity in several tumor types like renal cell carcinoma (Sternberg et al. J Clin Oncol 2009;27:abst. 5021), soft tissue sarcomas (Sleijfer et al. J Clin Oncol 2009;27:3126-32), hepatocellular carcinoma (Yau et al. J Clin Oncol 2009;27:abst. 3561), colorectal cancer (Brady et al. J Clin Oncol 2009;27:abst.4133), and thyroid cancers (Bible et al. J Clin Oncol 2009;27:abst. 3521). The Spanish Group for Research in Neuroendocrine Tumors (GETNE) group is an active Member inside of the GENET group and has a large tradition in clinical trials in NETs. The investigators hypothesize that pazopanib may have at least as good activity and better safety profile than other VEGFR inhibitors in progressive advanced or metastatic NET tumors derived from the digestive tract.

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