Clinical trial NCT02092714: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neuroendocrine Tumor
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-03-20
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with incurable neuroendocrine tumors, excluding small cell/large cell lung cancers and Merkel cell carcinomas

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.

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

Primary outcomes:
measure: Feasibility, defined as the true proportion of patients whose CancerCode sequencing results in the identification of at least 1 actionable mutation
timeFrame: Up to 3 years
Secondary outcomes:
measure: 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
timeFrame: Up to 3 years
measure: Progression-free survival
timeFrame: Up to 3 years
measure: Overall survival
timeFrame: Up to 3 years
measure: Proportion of Arm B patients whose therapy is changed as a result of physician access to CancerCode results
timeFrame: Up to 3 years
measure: Proportion of Arm B patients for whom a local protocol offers a potential therapeutic option based on CancerCode results
timeFrame: Up to 3 years
Other outcomes:
measure: Mutations occurring in greater than or equal to 10% of patients
timeFrame: Up to 3 years
measure: Mutations in the mTOR pathway
timeFrame: Up to 3 years
measure: Prognostic value of MGMT status among patients on alkylating agents
timeFrame: Up to 3 years
measure: Prognostic value of ERCC1 for patients on platinum-based regimens
timeFrame: Up to 3 years
measure: Prognostic value of TP for patients on fluoropyrimidine-based regimens
timeFrame: Up to 3 years
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Paul Engstrom
role: PRINCIPAL_INVESTIGATOR
References: