• Time to progression [ Designated as safety issue: No ]
  
• Progression-free survival at 4 months [ Designated as safety issue: No ]
  

• 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.

DISEASE CHARACTERISTICS:

• Histologically confirmed low-grade neuroendocrine neoplasm
• Measurable disease

• Radiographic evidence of disease progression after any prior systemic therapy, chemoembolization, bland embolization, or observation, defined by either of the following:

  • Appearance of a new lesion
  • At least 20% increase in the longest diameter of any previously documented lesion or in the sum of the longest diameters of multiple lesions
• Tissue block from original diagnostic or surgical specimen required
• Concurrent stable-dose octreotide required
• No small cell lung cancer, medullary thyroid cancer, paraganglioma, or pheochromocytoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be able to receive a contrast-enhanced CT scan
• No known history of allergic reactions to AMG 706 or derivatives or to octreotide injections
• No gastrointestinal tract disease resulting in an inability to take oral medication (i.e., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, bowel obstruction, or inability to swallow tablets)
• No requirement for IV alimentation
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³
• Hemoglobin level ≥ 8.0 g/dL
• Bilirubin ≤ 2.0 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver metastases are present)
• LVEF ≥ institutional lower limit of normal as evaluated by echocardiography or MUGA scan

• No history of uncontrolled hypertension (resting blood pressure > 150/90 mm Hg)

  • Antihypertensive medications allowed if patients is stable on their current dose

• No history of the following within the past 12 months:

  • New York Heart Association class III or IV congestive heart failure
  • Unstable angina pectoris
  • Myocardial infarction
  • Symptomatic cardiac arrhythmia
  • Cerebrovascular accident or transient ischemic attack
• No history of arterial or venous thrombosis within the past 12 months

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• One prior systemic chemotherapy regimen for low-grade neuroendocrine neoplasm allowed

  • Chemoembolization is not considered systemic chemotherapy
• At least 4 weeks since prior major surgery, chemotherapy, radiation therapy, other systemic therapy, or local liver therapy
• No prior procedures that would adversely affect intestinal absorption
• No prior anti-vascular endothelial growth factors
• No concurrent chemotherapy or radiation therapy