Cross-Platform Biomarker Program for Establishment and Validation of Liquid Biopsy for Clinical Decision Making in resectable gastrointestinal stromal tumour (GIST)

Cross-Platform Biomarker Program for Establishment and Validation of Liquid Biopsy for Clinical Decision Making in resectable gastrointestinal stromal tumour (GIST)

Gastrointestinal Stromal Tumor

Not yet recruiting

Start Date 05/01/2022

Age of Trial (yrs) 1.6

First-line Gleevec-resistant Adjuvant Neoadjuvant

none

Targeted therapy

Specifically GIST and only GIST

DRKS-ID: DRKS00023192

Universitätsklinikum Schleswig-Holstein Klinik für Hämatologie und Onkologie Campus Lübeck Prof. Dr. med. Nikolas von Bubnoff

Universitätsklinikum Schleswig-Holstein Campus Lübeck Emilia Prieß Ratzeburger Allee 160 23538 Lübeck Germany Telephone: +49-451-500-44355 nikolas.vonbubnoff@uksh.de

Despite optimal therapies, patients with gastrointestinal stromal tumours (GIST) can get relapses. High risk patients with certain genetic variants receive additional three-year medical treatment. But biomarkers for individual risk assessment are lacking. We previously demonstrated that pieces of genetic information (tumour DNA) can be detected in blood and that reduced levels are associated with ongoing therapeutic response. In this trial we investigate if tumour DNA will act as diagnostic marker for assessing relapse risk and those patients profiting of additional therapy. Prior, during initial therapy and at follow-up examinations every three months blood samples will be taken to measure Tumour DNA levels and detect genetic variants, that are responsible for a lack of response. Moreover, the protein profile in blood and the radiologic imaging data are getting analyzed in order to identify new biomarkers and predicting the risk of relapse.
In this trial high risk GIST patients with certain genetic variants are included to recognize relapses earlier and predict its risk better, so that only those patients who need and profit of additional therapy will get it



Arm 1:
Day -30 to -1 prior to start of therapy: Screening examination for all participants. A mutational analysis of a histologic sample is performed to detect cKIT- and PDGFR-mutations (inclusion criteria). Additionally imaging methods according to local standards are performed, blood samples will be taken and participants registered.

Participants with cKIT- and/or PDGFR-mutated tumours are further included:
During neoadjuvant therapy and during surgical therapy:
Day -1 to 0: Blood taking for ctDNA and proteins
Day +6 (±2): Blood taking for ctDNA and proteins
Day +14 (±2): Blood taking for ctDNA and proteins

After surgical therapy:
Month +3 to +60, every three months (± 28 d): imaging, blood taking for ctDNA and proteins

The current medication and disease stage is ascertained at every visit. The taken blood volume is 63 mL each.


Inclusion Criteria

Sex:
All

Minimum Age:
18 Years

Maximum Age:
no maximum age

Additional Inclusion Criteria:
• histologically confirmed GIST and finding of cKIT or PDGFR mutation in tissue
• localized, locally advanced or limited metastatic GIST disease
• high risk of relapse according to AFIP criteria
• planned resection, including local resection and multivisceral resection aiming for complete resection
• planned follow-up visits according to the current national guidelines (including standard of care imaging)
• ≥ 18 years

* Neoadjuvant treatment and adjuvant treatment after resection are allowed after admission.

Exclusion Criteria

• locally advanced or metastatic disease not amenable to curative surgery
• additional tumor disease in the past 3 years except for cervical carcinoma treated in line with guidelines or basal cell carcinoma and squamous cell carcinoma of the skin
• life expectancy < 3 months
• lack of cKIT or PDGFRA mutation in tissue