Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers

Neuroendocrine malignancies such as pancreatic neuroendocrine tumors (PNETs) and
gastrointestinal (GI) carcinoids, are generally rare but their incidences are increasing. In
vitro and in vivo studies have shown that proteasome inhibitors have activity against a
variety of tumor types. Carfilzomib (Kyprolis®) is an irreversible proteasome inhibitor with
a favorable safety profile that has been studied in a variety of hematologic and solid
tumors. Carfilzomib received accelerated approval from the U.S. FDA in 2012, based on a
favorable response rate, for the treatment of patients with multiple myeloma who received at
least two prior therapies, and demonstrated disease progression within 60 days of completing
the last therapy. In this multi-center study, the investigators propose to evaluate
carfilzomib for the treatment of patients with advanced neuroendocrine cancers.

Inclusion Criteria:

1. Adults with biopsy-proven advanced, unresectable or metastatic, well-to-moderately
differentiated (or low grade) neuroendocrine carcinoma, including typical carcinoid,
pancreatic islet cell and other well-to-moderately differentiated neuroendocrine
carcinomas.

2. Measurable disease per Response Evaluation Criteria in Solid Tumors RECIST v 1.1
criteria.

3. Patients currently receiving or previously treated with single agent sandostatin LAR®
are eligible. However, this is not a mandatory criterion to be included in the study.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

5. Adequate hematologic, renal, and hepatic function.

6. Predicted life expectancy > 12 weeks.

Exclusion Criteria:

1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade
neuroendocrine carcinoma, adenocarcinoid, globlet cell carcinoid, atypical carcinoid,
anaplastic carcinoid, pulmonary neuroendocrine and small cell carcinoma are not
eligible.

2. Patients who had radiation therapy, hormonal therapy, biologic therapy,
investigational agents, or chemotherapy for cancer within 21 days or 5 half-lives of
any chemotherapy or biologic/targeted agent, whichever is longer, prior to first
treatment day of the study.

3. Concurrent severe, intercurrent illness including, but not limited to, ongoing or
active infection, or psychiatric illness/social situations that would impair the
ability of the patient to receive protocol treatment.

4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical
procedures ≤7 days. No waiting required following port-a-cath placement.

5. Previously untreated brain metastases. Patients who have received radiation or surgery
for brain metastases are eligible if therapy was completed at least 2 weeks prior to
study entry and there is no evidence of central nervous system disease progression,
mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.

6. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C.