Phase II open-label clinical trial of vatalanib (PTK/ZK) in patients with progressive neuroendocrine cancer.

14624 Background: Vatalanib inhibits vascular endothelial growth factor receptor (VEGFR) by binding to the intracellular kinase domain of all 3 VEGFRs. Neuroendocrine tumors (NETs) express VEGF receptors. Inhibiting VEGF with bevacizumab, sorafenib and sunitinib reduced time to progression or tumor size in some NET patients (pts). To determine vatalanib's tolerability and efficacy in NET pts, a trial was performed.,Eligibility criteria included pts who had biopsy-proven metastatic NE cancer, such as carcinoid or islet cell, and had rising biochemical markers on somatostatin analog therapy. Eligible pts had measurable lesions other than bone, a KPS > 60% and normal hematologic, renal and hepatic functions. Pts on octreotide therapy were required to be on a stable dose not exceeding 30 mg monthly of the LAR formulation. Initial dosing of vatalanib was 1,250 mg daily. Biochemical responses within a 90 day interval were the primary response criteria. Secondary endpoints included changes in radiographic and scintigraphic scans and safety.,Seventeen pts (9 males) were enrolled between 5/20/05 to 12/15/07. Eleven pts are evaluable for efficacy and 16 pts are evaluable for safety. One pt continues on therapy 16 mos and another 7 mos after study entry. One pt withdrew consent; 1 pt died of disease within 5 days of study entry; 1 pt was allergic to vatalanib. Four pts required a 10-28 day discontinuation for rising SGOT/SGPT, alkaline phosphatase and Grade2 proteinuria. Resumption of vatalanib at 1,000 mg daily was well tolerated in 1 pt and 750 mg in another. One pt developed carcinoid crises with fever, flushing, rising 5-HIAA accompanied by Grade 2 proteinuria. Grade 1 nausea occurred in 14 pts with antiemetics required for 2 pts. Divided vatalanib dosing resulted in less nausea in these 2 pts. A partial (>50% decrease in 5-HIAA) biochemical response was observed in 3 pts. The observed radiographic (CT scans) and scintigraphic (OctreoScan) responses in 10 pts have shown progressive disease in 1 pt and stable/minimal response in 9 pts. Accrual to this trial is ongoing.,Vatalanib is well tolerated in the majority of pts and results in a 30% biochemical partial response rate in NET pts with rising biochemical markers on somatostatin analog therapy. [Table: see text].