Primary Outcome Measures:
- Time to progression [ Designated as safety issue: No ]
- Progression-free survival at 4 months [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Objective response (complete or partial response, progressive disease, or stable disease) as measured by RECIST criteria [ Designated as safety issue: No ]
- Toxicity and tolerability [ Designated as safety issue: Yes ]
- Effect of AMG 706 on markers in tumor cells [ Designated as safety issue: No ]
OBJECTIVES:
Primary
- Determine the 4-month progression-free survival (PFS) of patients with low-grade neuroendocrine tumors treated with AMG 706.
Secondary
- Determine the response rate and overall survival of patients treated with this drug.
- Determine the toxicity and tolerability of this drug in these patients.
- Determine the effect of this drug on tumor perfusion by functional CT scan.
- Determine the effect of this drug on tumor markers (e.g., chromogranin A, 5-hydroxyindoleacetic acid, and gastrin) specific for neuroendocrine tumors.
- Determine the effect of this drug on serum vascular endothelial growth factor (VEGF) levels.
- Determine the expression of VEGF, VEGF receptor-2 (VEGFR-2), chromogranin A, human achaetescute homolog-1, and Notch1 markers of neuroendocrine tumors.
OUTLINE: This is a multicenter study.
Patients receive oral AMG 706 once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Plasma samples are collected at baseline, periodically during study treatment, and at 4 weeks after the completion of study treatment. Samples are used to determine plasma vascular endothelial growth factor (VEGF) levels. Gene expression of downstream markers of Raf kinase expression (raf, MEK, and ERK) as well as HASH1 and Notch1 are evaluated at baseline. Tumor tissue collected at diagnosis or prior surgery is examined by reverse transcriptase-polymerase chain reaction assay. Contrast CT scans are conducted at baseline, day 2 of course 1, and week 8 to assess tumor perfusion.
After the completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.