Molecular Analysis in Tissue Samples From Patients With Advanced or Metastatic Neuroendocrine Tumors

PRIMARY OBJECTIVES:

I. To perform gene panel sequencing of patients with neuroendocrine tumors under care at Fox
Chase Cancer Center for the purpose of identifying therapeutic targets and prognostic
markers.

II. To assess the feasibility of performing a clinical trial of molecularly matched therapy
in patients with differing subtypes of neuroendocrine tumors (neuroendocrine tumors of the
pancreas [PNETs], non-pancreatic neuroendocrine tumors [NETs], and poorly differentiated
NETs), based upon the proportion of patients with actionable mutations.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients whose therapy is altered based upon the results of
molecular testing.

II. To evaluate the percent of patients for which a local protocol offers a potential
therapeutic option.

III. To evaluate the number of patients who are treated based on therapy guided by molecular
profiling.

TERTIARY OBJECTIVES:

I. To compare the outcomes of patients treated with early therapy based on gene profiling
with the outcomes of those treated via National Cancer National Comprehensive Cancer Network
(NCCN) guideline recommended therapies (systemic therapy, liver directed therapy, hepatic
resection) or expectant observation via measurement of progression free survival (PFS), via
radiographic response rates, and via biochemical response rate.

II. To evaluate the prognostic power of commonly (>= 10%) detected mutations. III. To
evaluate the impact of mammalian target of rapamycin (mTOR) pathway alterations (mutations
of phosphatase and tensin homolog gene [PTEN], phosphatidylinositol-4,5-bisphosphate
3-kinase, catalytic subunit alpha [PIK3CA]) on efficacy of mTOR targeted therapeutics, as
assessed by progression free survival (PFS) and response rate (RR).

IV. To evaluate the impact of o-6-methylguanine-deoxyribonucleic acid (DNA)
methyltransferase (MGMT) status on the efficacy of an alkylating based chemotherapy regimen
(Temodar, dacarbazine, streptozocin), as assessed by progression free survival (PFS) and
response rate (RR).

V. To evaluate the impact of thymidine phosphorylase (TP) status on the efficacy of a
fluoropyrimidine-based chemotherapy regimen (capecitabine, 5-fluorouracil), as assessed by
progression free survival (PFS) and response rate (RR).

VI. To evaluate the impact of excision repair cross-complementing 1 (ERCC-1) status on the
efficacy of a platinum-based chemotherapy regimen (carboplatin, cisplatin, oxaliplatin), as
assessed by progression free survival (PFS) and response rate (RR).

OUTLINE:

Previously collected tissue samples are analyzed via mutational sequencing and
immunohistochemistry.

After completion of study, patients are followed for up every 3-6 months for 3 years.

Inclusion Criteria:

- Pathologically or cytologically confirmed neuroendocrine tumor which is metastatic,
locally advanced or otherwise incurable (of any grade or primary site, excluding
small cell lung cancers, large cell lung cancers, and Merkel cell carcinomas)

- Evaluable disease by radiographic imaging

- Adequate available tumor tissue (formalin-fixed paraffin-embedded [FFPE] tissue or
cytologic material) for sequencing (containing > 50% tumor cellularity by
histopathology) or consent to tumoral biopsy for fresh tissue; adequacy will be
determined by our pathology department, under supervision of Dr. Gustafson

- Ability to understand and willingness to sign a written informed consent and Health
Information Portability and Accountability Act (HIPAA) consent document

- Life expectancy of >= 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2

Exclusion Criteria:

- Localized neuroendocrine tumor for which the patient is eligible for a potentially
curative surgical intervention

- Primary diagnosis of pulmonary small cell carcinoma, pulmonary large cell carcinoma
or Merkel cell carcinoma

- Inability to provide informed consent

- Inadequate tissue available for genetic testing

- Any secondary active malignancy, excluding non-melanoma skin cancers; if the
patient's prognosis will be primarily determined by their neuroendocrine tumor, the
secondary malignancy is to be discounted