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

A Pilot Study Utilizing Molecular Analysis Via Cancer CodeTM to Identify Therapeutic Targets for Patients With Advanced 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.

Study Overview

• Status: Unknown
• Conditions: Neuroendocrine Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis

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.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with incurable neuroendocrine tumors, excluding small cell/large cell lung cancers and Merkel cell carcinomas

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-correlative (molecular analysis); Previously collected tissue samples are analyzed via mutational sequencing and immunohistochemistry.	Other: laboratory biomarker analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Feasibility, defined as the true proportion of patients whose CancerCode sequencing results in the identification of at least 1 actionable mutation	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate, defined as at least a 30% decrease in target lesions when measureable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria	The response rate (with 95% two-sided confidence intervals) will be computed for all Arm B patients and separately for pre-specified subgroups (e.g., molecular profile-based treatment vs. NCCN guideline recommended).	Up to 3 years
Progression-free survival	Progression-free survival time will be characterized for all Arm B patients and separately for pre-specified subgroups (e.g., molecular profile-based treatment vs. NCCN guideline recommended) using the method of Kaplan and Meier.	Up to 3 years
Overall survival	Overall survival time will be characterized for all Arm B patients and separately for pre-specified subgroups (e.g., molecular profile-based treatment vs. NCCN guideline recommended) using the method of Kaplan and Meier.	Up to 3 years
Proportion of Arm B patients whose therapy is changed as a result of physician access to CancerCode results		Up to 3 years
Proportion of Arm B patients for whom a local protocol offers a potential therapeutic option based on CancerCode results		Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutations occurring in greater than or equal to 10% of patients	Log-rank test and Kaplan-Meier plots will be used to assess the relationships between progression free interval and common mutations (>= 10%) or immunohistochemistry (IHC) test results in the entire population.	Up to 3 years
Mutations in the mTOR pathway	Log-rank test and Fisher's exact tests will be used to assess the relationships between mutations in the mTOR pathway and progression free interval or response among Arm B patients treated with mTOR inhibitors.	Up to 3 years
Prognostic value of MGMT status among patients on alkylating agents		Up to 3 years
Prognostic value of ERCC1 for patients on platinum-based regimens		Up to 3 years
Prognostic value of TP for patients on fluoropyrimidine-based regimens		Up to 3 years

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paul Engstrom, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2013
• Primary Completion (Actual): April 11, 2018
• Study Completion (Anticipated): November 16, 2020

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 18, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: CGI-061; P30CA006927 (U.S. NIH Grant/Contract); NCI-2013-01950 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 13-040 (Fox Chase Cancer Center)