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

NCT06541080 | Recruiting DMC

• 1 other identifier: B3002021000275
• Study Type: observational
• Target: 550
• Locations: 1 country
• Sites: 8

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.

Conditions

Neuroendocrine Neoplasms

Keywords

liquid biopsy; circulating cell-free DNA; methylation-based biomarkers

Outcome Measures

Primary Outcomes (3)

• Validating novel ccfDNA analyzing techniques for assessment of the presence and quantification of ctDNA in liquid biopsies derived from NEN patients

  ctDNA fraction

  5 years after informed consent form (ICF) signature

• Monitoring tumor fraction over time in sequential plasma samples from NEN patients using ccfDNA assays

  ctDNA quantities

  5 years after ICF signature

• Correlate tumor fraction with time to progression (according to RECIST 1.1 criteria)

  tumor fraction

  5 years after ICF signature

Study Arms (2)

Regular Sampling Group (RSG)

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.

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

Intensive Sampling Group (ISG)

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.).

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

Interventions

Shallow Whole Genome Sequencing (sWGS)-GIPXplore DIAGNOSTIC_TEST

GIPXplore will be used to mine shallow whole genome sequencing cell free DNA data for identification of signatures.

Intensive Sampling Group (ISG); Regular Sampling Group (RSG)

methylation-sensitive restriction enzymes (MSRE)-Single-molecule molecular inversion probes (smMIP)-seq assay DIAGNOSTIC_TEST

Aberrant methylation in ccfDNA will be analyzed using the novel, highly sensitive MSRE-smMIP-seq technology.

Intensive Sampling Group (ISG); Regular Sampling Group (RSG)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

NEN patients

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Universiteit Antwerpen: collaborator
• KU Leuven: collaborator

Study Sites (8)

AZ Rivierenland

Rumst, Antwerp, Belgium

NOT YET RECRUITING

VITAZ

Sint-Niklaas, East-Flanders, Belgium

NOT YET RECRUITING

University Hospital Leuven

Leuven, Flemish Brabant, Belgium

NOT YET RECRUITING

Ziekenhuis Netwerk Antwerpen (ZNA)

Antwerp, 2020, Belgium

NOT YET RECRUITING

Gasthuiszusters Ziekenhuizen (GZA)

Antwerp, 2610, Belgium

NOT YET RECRUITING

AZ Monica

Antwerp, Belgium

NOT YET RECRUITING

AZ Klina

Brasschaat, 2930, Belgium

NOT YET RECRUITING

Antwerp University Hospital (UZA)

Edegem, 2650, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample

Study Officials

• Timon Vandamme

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siddharth Chhajlani

CONTACT

03436; siddharth.chhajlani@uantwerpen.be

isolde Van der Massen

CONTACT

03821; netwerkstudies@uza.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: August 7, 2024
• Study Start: January 3, 2022
• Primary Completion (Estimated): December 4, 2028
• Study Completion (Estimated): December 4, 2030
• Last Updated: August 7, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (8)