Surgical Intervention and the NETest (NETest_Sx)

Diagnosis of Neuroendocrine Neoplasms and Assessment of Response to Surgery by Means of Measurement of Gene Transcripts in Blood

The purpose of this study is to evaluate the effect of different surgical resections (R0, R1, R2) on circulating NET transcripts (PCR score or NETest). A drop in circulating NET levels will be correlated with surgical excision. Secondly, variation of circulating NET transcripts will be correlated to NET recurrence to test whether this analysis may constitute an early predictive marker of disease relapse.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumor; Gastroenteropancreatic
• Intervention / Treatment: Procedure: Surgery

Detailed Description

Biomarker-based tools that can accurately predict gastroenteropancreatic neuroendocrine tumor (GEP-NET) treatment response and tumor recurrence are currently not available. Circulating biomarkers that are associated with GEP-NETs are limited to measurements of plasma chromogranin A (CgA). The investigators have developed a PCR-based tool to quantitate (score) the circulating GEP-NET molecular signature ("liquid" biopsy) with high sensitivity and specificity. This signature can identify all types of GEP-NETs including small (1cm) non-metastatic tumors, is significantly reduced after tumor debulking and is decreased following surgical "cure". Elevated post-surgical scores are associated with tumor recurrence within 6 months in ~40% of cases. Current NET treatment protocols are associated with tumor recurrence (progression free survival) ranging from 5-18 months. The majority of patients will experience a relapse within 18 months irrespective of the treatment approach. The investigators hypothesize that a PCR measurement of circulating NET mRNA can accurately predict the extent of surgical resection (tumor removal) and elevated scores can predict tumor relapse before this occurs. This biomarker protocol seeks to test this hypothesis and evaluate whether changes in plasma CgA are as effective in predicting resection and recurrence.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20132
    • San Raffaele Hospital IRCCS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed, well differentiated (G1, G2 or G3), local and advanced (metastatic), neuroendocrine tumor of gastro-enteropancreatic origin.
• Treatment-naïve as well as patients who have received previous therapies.
• Patients currently on LAR with clinically stable disease.
• CT or MRI documentation of disease.
• WHO performance status ≤2.

Exclusion Criteria:

• Known history of HIV seropositivity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Post Surgery	Procedure: Surgery; Surgical excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker prediction of tumor recurrence	Analysis of the alterations in the biomarker levels (from post-surgical levels, i.e., month 1) will be utilized to establish when the disease status has altered; a sustained increase in score will be recorded and compared with imaging to assess whether this is associated with disease progression/recurrence.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers and clinical symptomatology	Biomarker scores will be compared to the frequency of clinical symptoms, specifically flushing, to assess whether there is a relationship.	24 months
Biomarkers and clinical symptomatology	Biomarker scores will be compared to the frequency of clinical symptoms, specifically diarrhea, to assess whether there is a relationship.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alteration in biomarkers and tumor removal	Analysis of the change in biomarker scores (from baseline to post-surgical levels at 1 month) will be utilized to establish the strength of the relationship between the biomarker and volume of tumor removed (cm3).	24 months

Collaborators and Investigators

• Sponsor: Wren Laboratories LLC

Publications and helpful links

General Publications

• Modlin IM, Frilling A, Salem RR, Alaimo D, Drymousis P, Wasan HS, Callahan S, Faiz O, Weng L, Teixeira N, Bodei L, Drozdov I, Kidd M. Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2016 Jan;159(1):336-47. doi: 10.1016/j.surg.2015.06.056. Epub 2015 Oct 9.
• Modlin IM, Kidd M, Bodei L, Drozdov I, Aslanian H. The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract. Am J Gastroenterol. 2015 Aug;110(8):1223-32. doi: 10.1038/ajg.2015.160. Epub 2015 Jun 2.
• Oberg K, Modlin IM, De Herder W, Pavel M, Klimstra D, Frilling A, Metz DC, Heaney A, Kwekkeboom D, Strosberg J, Meyer T, Moss SF, Washington K, Wolin E, Liu E, Goldenring J. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015 Sep;16(9):e435-e446. doi: 10.1016/S1470-2045(15)00186-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2017
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (ESTIMATE): January 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

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: Surgery_NETest

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No