Molecular Analysis in Tissue Samples From Patients With Advanced or Metastatic Neuroendocrine Tumors
Molecular Analysis in Tissue Samples From Patients With Advanced or Metastatic Neuroendocrine Tumors
This pilot research trial studies molecular analysis in tissue samples from patients with
 advanced or metastatic neuroendocrine tumors. Studying samples of tissue from patients with
 neuroendocrine tumors in the lab may help doctors identify mutations to classify disease and
 plan the best treatment.
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