A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors

Inclusion Criteria

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 acetate 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
acetate 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