AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

Neuroendocrine tumors (NETs) comprise a heterogeneous spectrum of neoplasms. NETs are
commonly subclassified into two broad subgroups according to their site of origin: pancreatic
NETs are thought to arise from the endocrine cells of the pancreas, whereas NETs of other
sites such as the lungs or gastrointestinal tract are often referred to as carcinoid tumors.
While histologically similar, carcinoid tumors and pancreatic neuroendocrine tumors have
demonstrated different response rates in prior phase II studies of antitumor agents. Because
of these differences, we will perform the current study using two cohorts of patients (30
with carcinoid and 30 with pancreatic neuroendocrine tumors). The statistical design,
however, is the same for both cohorts. With 30 patients in each cohort, this study has 80%
power assuming type I error of 6% to differentiate a >/=17% objective response rate from a
promising in either cohort if at least 4 of 30 patients achieve an objective response.

Inclusion Criteria:

- Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors. To
be classified as having a pancreatic neuroendocrine tumor, patients must have clinical
evidence of currently having or having had a primary pancreatic neuroendocrine lesion.

- Measurable disease by RECIST criteria

- Evidence of progressive disease (by RECIST) within 12 months of study entry.

- Tumors must be considered well- or moderately-differentiated. Patients with poorly
differentiated neuroendocrine carcinoma of small cell carcinoma are excluded from this
study.

- Adequate hepatic, renal, bone marrow and glycemic function as outlined in the protocol

- Prior treatment with chemotherapy, hepatic artery embolization, surgery or other
therapeutic agents is allowed.

- Prior or concurrent therapy with somatostatin analogs is permitted: however patients
must continue on a stable dose of somatostatin analogs while receiving study
treatment.

- 18 years of age or older

- ECOG performance status 0, 1, or 2 [Eastern Cooperative Oncology Group ]

- Life expectancy of at least 12 weeks

- Negative pregnancy test

- Ability to sign informed consent

Exclusion Criteria:

- Poorly differentiated or small cell neuroendocrine carcinomas

- Insulin secreting pancreatic neuroendocrine tumors (insulinomas)

- Clinically apparent central nervous system metastases or carcinomatous meningitis.

- Myocardial infraction in the past 6 months

- Major surgery 4 weeks prior to enrollment

- Uncontrolled serious medical or psychiatric illness

- Pregnant or lactating women. Both men and women of childbearing potential must be
advised of the importance of using effective birth control measures during the course
of the study.

- Prior antitumor therapy within 4 weeks of enrollment (with the exception of
somatostatin analogs).

- Recent infection requiring systemic anti-infective treatment that was completed 14
days or less prior to enrollment (with the exception of uncomplicated urinary tract
infection or upper respiratory tract infection).

- Known positive test for human immunodeficiency virus, hepatitis C, chronic or active
hepatitis B

- Prior IGF or IGF receptor inhibitor therapy [insulin like growth factor ]