Surgical Intervention and the NETest

Neuroendocrine Tumor Clinical Trial

— NETest_Sx  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03012789
• Other study ID #: Surgery_NETest
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 15, 2017
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Wren Laboratories LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastroenteropancreatic
• Neuroendocrine Tumor
• Neuroendocrine Tumors

Intervention

Procedure:
• Surgery
Surgical excision

Locations

Country	Name	City	State
Italy	San Raffaele Hospital IRCCS	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Wren Laboratories LLC

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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 strate — View Citation

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/aj — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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