Collection of Liquid Biopsy Samples of Neuroendocrine Neoplasms (NEN) Patients - Collection of NET (CollectNET) 2.0, a Study by the BE-FORCE Consortium

Recruiting

• Conditions: Neuroendocrine Neoplasms
• Interventions: Diagnostic Test: Shallow Whole Genome Sequencing (sWGS)-GIPXplore; Diagnostic Test: methylation-sensitive restriction enzymes (MSRE)-Single-molecule molecular inversion probes (smMIP)-seq assay

• Registration Number: NCT06541080
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

The CollectNET 2.0 by BE-FORCE is a prospective, multicentric, interventional study in which liquid biopsies will be collected from neuroendocrine neoplasms (NEN) patients to create an extensive biobank that will be used for current and future circulating cell-free DNA (ccfDNA) analyses. Two sampling groups will be created: the "Regular Sampling Group" and the "Intensive Sampling Group". Upon participation, up to four additional blood tubes (max. total of 32.5mL) will be collected at each timepoint as specified below. These include 3 Streck Cell-Free DNA tubes (10 mL each) which will be used for the extraction of ccfDNA and 1 PreAnalytiX (PAXgene)® Blood RNA tube (2.5 mL). All NEN patients in one of the participating hospitals who have measurable tumor burden on imaging will be asked to participate in our study and will be included in the "Regular Sampling Group". If additionally, the patient is (i) diagnosed with a histologically confirmed NEN of World Health Organisation (WHO) 2019 grade 1-3 neuroendocrine tumor (NET) or neuroendocrine carcinoma (NEC) from pancreatic, colorectal or small intestinal origin and (ii) is starting any kind of 1st line systemic treatment (e.g. somatostatin analogues, targeted therapy, chemotherapy, etc.), they will be followed up more intensively as per the "Intensive Sampling Group". If during follow-up in this "Intensive Sampling Group" patients have disease progression or have completed follow-up for 3 years in this group, their follow-up will switch back to the "Regular Sampling Group" for the remainder of the study. Ultimately, the samples collected in the "Intensive Sampling Group" will be used to achieve the second and third objective of our current project. These are to validate novel ccfDNA analyzing techniques (IMPRESS and GIPXplore) for assessment of the presence and quantification of circular tumor DNA (ctDNA) in liquid biopsies, and to monitor tumor fraction (i.e., ctDNA quantities) over time in sequential plasma samples from NEN patients using ccfDNA assays and correlating this with time to progression (according to RECIST 1.1 criteria) to explore the predictive efficacy of ccfDNA analysis and thereby evaluate its biomarker potential for patient follow-up. While samples from the "Regular Sampling Group" and the PAXgene tubes will be biobanked for future projects.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-03
• Status Verified: 2023-12
• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-08-01
• Last Update Submitted: 2024-08-01
• Study First Posted: 2024-08-07
• Last Update Posted: 2024-08-07
• Primary Completion: 2028-12-04
• Study Completion: 2030-12-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

• Male or female ≥ 18 years of age on the day of signing informed consent.
• Written informed consent must be obtained from the patient or patient's legal representative.
• Patient is willing and able (in the investigator's opinion) to comply with all trial requirements.
• For inclusion in the Regular Sampling Group: patients must have (had) a histologically confirmed NEN diagnosis, patients must have measurable tumor burden on imaging, patients must be in follow-up in one of the participating hospitals and patients who have progressed or completed follow-up for 3y in the Intensive Sampling Group.
• For inclusion in the Intensive Sampling Group: patients who are included in the Regular Sampling Group and where either a baseline sample (RSG-B) or a recent RSG follow-up sample (RSG-V...) has been collected before the start of 1st systemic treatment (as defined below), patients must be diagnosed with a histologically confirmed NEN diagnosis of a WHO 2019 grade 1-3 NET or NEC of pancreatic, colorectal, or small intestinal origin and patients must start any kind of 1st line systemic treatment (e.g. somatostatin analogues, targeted therapy, chemotherapy, etc.).

Exclusion Criteria

• Patients who are unable to give informed consent.
• Patients for which blood sampling would compromise their overall health.
• Patients pregnant at time of study entry or are willing to become pregnant during the study.
• Patients with a history or current evidence of any condition or abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Investigator.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intensive Sampling Group (ISG)	Shallow Whole Genome Sequencing (sWGS)-GIPXplore	This group consists of patients who at baseline or during the course of the study patients in this group (i) have a histologically confirmed NEN of WHO 2019 grade 1-3 NET or NEC from pancreatic, colorectal, or small intestinal origin and (ii) are starting any kind of 1st line systemic treatment (e.g. somatostatin analogues, targeted therapy, chemotherapy, etc.).
Intensive Sampling Group (ISG)	methylation-sensitive restriction enzymes (MSRE)-Single-molecule molecular inversion probes (smMIP)-seq assay	This group consists of patients who at baseline or during the course of the study patients in this group (i) have a histologically confirmed NEN of WHO 2019 grade 1-3 NET or NEC from pancreatic, colorectal, or small intestinal origin and (ii) are starting any kind of 1st line systemic treatment (e.g. somatostatin analogues, targeted therapy, chemotherapy, etc.).
Regular Sampling Group (RSG)	Shallow Whole Genome Sequencing (sWGS)-GIPXplore	This group consists of all NEN patients who have measurable tumor burden on imaging (and who do not fulfill the criteria for the Intensive Sampling Group) and are willing to participate in the study.
Regular Sampling Group (RSG)	methylation-sensitive restriction enzymes (MSRE)-Single-molecule molecular inversion probes (smMIP)-seq assay	This group consists of all NEN patients who have measurable tumor burden on imaging (and who do not fulfill the criteria for the Intensive Sampling Group) and are willing to participate in the study.

Primary Outcome Measures

Name	Time	Method
Validating novel ccfDNA analyzing techniques for assessment of the presence and quantification of ctDNA in liquid biopsies derived from NEN patients	5 years after informed consent form (ICF) signature	ctDNA fraction
Monitoring tumor fraction over time in sequential plasma samples from NEN patients using ccfDNA assays	5 years after ICF signature	ctDNA quantities
Correlate tumor fraction with time to progression (according to RECIST 1.1 criteria)	5 years after ICF signature	tumor fraction

Trial Locations

Locations (8)

AZ Rivierenland; 🇧🇪 Rumst, Antwerp, Belgium

AZ Klina; 🇧🇪 Brasschaat, Belgium

University Hospital Leuven; 🇧🇪 Leuven, Flemish Brabant, Belgium

Antwerp University Hospital (UZA); 🇧🇪 Edegem, Belgium

VITAZ; 🇧🇪 Sint-Niklaas, East-Flanders, Belgium

Ziekenhuis Netwerk Antwerpen (ZNA); 🇧🇪 Antwerpen, Belgium

Gasthuiszusters Ziekenhuizen (GZA); 🇧🇪 Antwerpen, Belgium

AZ Monica; 🇧🇪 Antwerpen, Belgium