AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors

Inclusion Criteria

• 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 acetate required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be able to receive a contrast-enhanced CT scan
• 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)
• Aspartate aminotransferase (AST) ≤ 3 times ULN (5 times ULN if liver metastases are present)
• Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit of normal as evaluated by echocardiography or multigated acquisition (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
• 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

Exclusion criteria

• Prior procedures that would adversely affect intestinal absorption
• Prior anti-vascular endothelial growth factors
• Concurrent chemotherapy or radiation therapy
• 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
• Arterial or venous thrombosis
• Known history of allergic reactions to AMG 706 or derivatives or to octreotide acetate injections
• 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)
• Pregnant or nursing
• Small cell lung cancer, medullary thyroid cancer, paraganglioma, or pheochromocytoma
• Requirement for intravenous alimentation