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

• ClinicalTrials.gov Identifier: NCT02092714
• Recruitment Status: Active, not recruiting
• First Posted: March 20, 2014
• Last Update Posted: July 23, 2019
• Sponsor: Fox Chase Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Fox Chase Cancer Center

Tracking Information

• First Submitted Date: March 18, 2014
• First Posted Date: March 20, 2014
• Last Update Posted Date: July 23, 2019
• Actual Study Start Date: October 16, 2013
• Actual Primary Completion Date: April 11, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 18, 2014): Feasibility, defined as the true proportion of patients whose CancerCode sequencing results in the identification of at least 1 actionable mutation [ Time Frame: Up to 3 years ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02092714 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 18, 2014)

• 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 [ Time Frame: Up to 3 years ]
  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).
• Progression-free survival [ Time Frame: Up to 3 years ]
  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.
• Overall survival [ Time Frame: Up to 3 years ]
  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.
• Proportion of Arm B patients whose therapy is changed as a result of physician access to CancerCode results [ Time Frame: Up to 3 years ]
• Proportion of Arm B patients for whom a local protocol offers a potential therapeutic option based on CancerCode results [ Time Frame: Up to 3 years ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 18, 2014)

• Mutations occurring in greater than or equal to 10% of patients [ Time Frame: Up to 3 years ]
  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.
• Mutations in the mTOR pathway [ Time Frame: Up to 3 years ]
  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.
• Prognostic value of MGMT status among patients on alkylating agents [ Time Frame: Up to 3 years ]
• Prognostic value of ERCC1 for patients on platinum-based regimens [ Time Frame: Up to 3 years ]
• Prognostic value of TP for patients on fluoropyrimidine-based regimens [ Time Frame: Up to 3 years ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Molecular Analysis in Tissue Samples From Patients With Advanced or Metastatic Neuroendocrine Tumors
• Official Title: A Pilot Study Utilizing Molecular Analysis Via Cancer CodeTM to Identify Therapeutic Targets for Patients With Advanced Neuroendocrine Tumors
• 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

blood and tumor tissue

• Sampling Method: Non-Probability Sample
• Study Population: Patients with incurable neuroendocrine tumors, excluding small cell/large cell lung cancers and Merkel cell carcinomas
• Condition: Neuroendocrine Tumor

Intervention

Other: laboratory biomarker analysis

Correlative studies

Study Groups/Cohorts

Ancillary-correlative (molecular analysis)

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

Intervention: Other: laboratory biomarker analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 18, 2014): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 16, 2020
• Actual Primary Completion Date: April 11, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02092714
• Other Study ID Numbers: CGI-061; NCI-2013-01950 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 13-040 ( Other Identifier: Fox Chase Cancer Center ); P30CA006927 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Fox Chase Cancer Center
• Study Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Engstrom; Fox Chase Cancer Center

• PRS Account: Fox Chase Cancer Center
• Verification Date: July 2019