Clinical trial NCT03012789: Surgical Intervention and the NETest
Official title: Diagnosis of Neuroendocrine Neoplasms and Assessment of Response to Surgery by Means of Measurement of Gene Transcripts in Blood
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Neuroendocrine Tumor
Gastroenteropancreatic
Lead sponsor: Wren Laboratories LLC
Sponsor class: INDUSTRY
First posted: 2017-01-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Biomarker prediction of tumor recurrence
timeFrame: 24 months
Secondary outcomes:
measure: Biomarkers and clinical symptomatology
timeFrame: 24 months
measure: Biomarkers and clinical symptomatology
timeFrame: 24 months
Other outcomes:
measure: Alteration in biomarkers and tumor removal
timeFrame: 24 months
Locations:
city: Milano
country: Italy
facility: San Raffaele Hospital IRCCS
Study officials:
References:
citation: 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.
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/ajg.2015.160. Epub 2015 Jun 2.
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;16(9):e435-e446. doi: 10.1016/S1470-2045(15)00186-2.