CIRculating Cell-free nUcLeic Acids in Cancer Therapy Monitoring -01

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
CIRculating Cell-free nUcLeic Acids in Cancer Therapy Monitoring -01

Conditions
-----------------
Next-Generation-Sequencing

Intervention / Treatment
-----------------
* Genetic: Molecular genetic diagnostic


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Molecular genetic diagnostic<br>Next-Generation-Sequencing (NGS)-methods | Genetic: Molecular genetic diagnostic<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Next-Generation-Sequencing, Cell free DNA, Cell free RNA, Circulating tumor DNA, Circulating tumor RNA, Course of therapy