CIRculating Cell-free nUcLeic Acids in Cancer Therapy Monitoring -01 (CIRCULATING-01)

In cooperation with the molecular tumor board of the University Hospital Tübingen (UKT), a prospective collection of blood samples during the course of therapy is planned. It is a pilot study in which the technical feasibility of the approach (Highly Sensitive Next-Generation Sequencing (NGS) methods) initially should to be evaluated and further developed.

Study Overview

• Status: Not yet recruiting
• Conditions: Next-Generation-Sequencing
• Intervention / Treatment: Genetic: Molecular genetic diagnostic

Detailed Description

In this study, we would like to use and further develop Highly Sensitive Next-Generation Sequencing (NGS) methods. For this purpose, circulating cell-free nucleic acids (cell free desoxyribonucleic acid (cfDNA) or cell free ribonucleic acid (cfRNA)) are first isolated from the blood plasma. The circulating tumor desoxyribonucleic acid (ctDNA) and circulating tumor ribonucleic acid (ctRNA) fractions contained therein arise from the tumor tissue and can provide information about the existing tumor burden and the original tissue of the tumor. Somatic Single Nucleotide Variants (SNVs) and insertions and deletions (indels) serve as biomarkers within the ctDNA and ctRNA. The ctDNA also contains epigenetic information in the form of DNA methylation, which shows a characteristic pattern for each tissue. Informative regions of the genome can be specifically enriched using personalized or fixed NGS panels. In this way, an ultra-deep sequencing of defined regions can be carried out and even the smallest concentrations of ctDNA and ctRNA in liquid biopsies can be detected.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Schroeder, Dr.; Phone Number: 72296 +49 7071 29; Email: christopher.schroeder@med.uni-tuebingen.de
• Study Contact Backup: Name: Julian Broche, Dr.; Phone Number: 61298 +49 7071 29; Email: julian.broche@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Advanced tumor disease
• Ability to consent
• Existence of a declaration of consent signed by the patient and physician (informed consent for study participation and Comprehensive Cancer Center (CCC) biobank
• Existence or planned implementation of tumor-normal sequencing (usually carried out in a diagnostic context upon presentation at the Molecular Tumor Board (MTB)

Exclusion Criteria:

- No therapy recommendation by MTB

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Molecular genetic diagnostic; Next-Generation-Sequencing (NGS)-methods

Genetic: Molecular genetic diagnostic; With the help of modern, highly sensitive analysis methods (NGS), such as ultra-low high-throughput sequencing, even the smallest amounts of circulating cell-free nucleic acids in the blood can be detected. In the individual course of therapy, the changes in concentration of the tumor-specific variants can thus be continuously monitored and appropriate therapy decisions can be made. The presence of minimal residual diseases and the development of resistance mutations can also be examined using this technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cfDNA/cfRNA	Ratio of cfDNA/cfRNA preoperative	Day 1: Preoperative
cfDNA/cfRNA	Ratio of cfDNA/cfRNA during therapy	Day 2: At intervals of approx. 6-10 weeks
cfDNA/cfRNA	Ratio of cfDNA/cfRNA at recurrence or disease progression	Day 3: Tumor recurrence or disease progression

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: German Consortium for Translational Cancer Research
• Investigators: Principal Investigator: Christopher Schroeder, Dr., University Hospital Tübingen; Study Chair: Stephan Ossowski, Prof. Dr., University Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2023
• Primary Completion (Anticipated): October 1, 2025
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Circulating tumor DNA; Cell free DNA; Cell free RNA; Next-Generation-Sequencing; Circulating tumor RNA; Course of therapy
• Other Study ID Numbers: CIRCULATING-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The CIRCULATION-01 study will provide data in a pseudonymized manner to national and international databases set up to increase the diagnostic yield through advanced analysis tools.
• IPD Sharing Time Frame: Data will become available after analysis and unlimited.
• IPD Sharing Access Criteria: Authorized users within the participating organizations.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

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