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

NCT ID: NCT02092714

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-10-16
• Study Completion Date: 2020-11-16

Brief Summary

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.

Detailed Description

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.

Conditions

Neuroendocrine Tumor

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Ancillary-correlative (molecular analysis)

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

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fox Chase Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Engstrom

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

NCI-2013-01950

Identifier Type: REGISTRY

Identifier Source: secondary_id

13-040

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA006927

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CGI-061

Identifier Type: -

Identifier Source: org_study_id