Cross-Platform Biomarker Program for Establishment and Validation of Liquid Biopsy for Clinical Decision Making in resectable gastrointestinal stromal tumour (GIST)
Organizational Data
- DRKS-ID:
- DRKS00023192
- Recruitment Status:
- Recruiting planned
- Date of registration in DRKS:
- 2021-06-30
- Last update in DRKS:
- 2022-03-16
- Registration type:
- Prospective
Acronym/abbreviation of the study
Liquid biopsy in resectable GIST
URL of the study
No Entry
Brief summary in lay language
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.
Brief summary in scientific language
In cases of GIST, risk of relapse after resection is assessed using clinicopathological criteria, including tumor size, localization and mitotic index according to AFIP criteria[1]. Patients with high risk of relapse and a tumor mutation responsive to tyrosine kinase inhibitor will receive three-year adjuvant treatment with e.g. imatinib. But biomarkers for individual risk assessment are lacking. We have previously demonstrated that circulating tumor (ct)DNA can be detected in plasma samples of patients with localized and metastatic disease [2], and that a reduced ctDNA level is associated with ongoing therapeutic response [3]. In this trial, we aim to examine ctDNA in blood of study subjects with localised, locally advanced or limited metastatic GIST and high AFIP risk of relapse via dPCR (digital PCR) and NGS. We will investigate whether the amount of mutant ctDNA is informative with respect to clinical endpoints such as risk of relapse or response to (neo-) adjuvant pharmacotherapy. Additionally, we will analyse the proteome in blood of study subjects to detect further biomarker for risk stratification and monitoring of therapeutic response. Furthermore, in case of relapse we will search for secondary mutation in ctDNA via multiplex-PCR and NGS which might be responsible for resistance to pharmacotherapy. This aims to investigate the impact of clonal heterogeneity at the time of diagnosis and relapse. Moreover, imaging can also reveal potential prognostic information, that are not visual to investigators. In this context radiologic imaging data are going to analyzed by radiomics, meaning computer based analysis methods, to gain information about the aggressiveness of the tumour, the clinical course and the response to therapy.
Health condition or problem studied
- ICD10:
- C15 - Malignant neoplasm of oesophagus
- ICD10:
- C16 - Malignant neoplasm of stomach
- ICD10:
- C17 - Malignant neoplasm of small intestine
- ICD10:
- C18 - Malignant neoplasm of colon
- ICD10:
- C48 - Malignant neoplasm of retroperitoneum and peritoneum
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- 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.
Endpoints
- Primary outcome:
- 1. detection of tumor-specific mutations in ctDNA isolated from plasma after surgical therapy
- Secondary outcome:
- 1. detection of tumor-specific mutations in ctDNA isolated from plasma at diagnosis 2. detection of tumor-specific mutations in ctDNA isolated from plasma before surgical therapy 3. detection of tumor-specific mutations in ctDNA isolated from plasma before neoadjuvant pharmacotherapy 4. dynamic changes in the amount of ctDNA during and after neoadjuvant pharmacotherapy 5. dynamic changes in the amount and composition of ctDNA during trial duration 6. amount of ctDNA/MAF (minor allele frequency) in case of high risk of relapse calculated via AFIP-score 7. changes in the amount of ctDNA/MAF in case of clinically diagnosed progressive disease or relapse 8. changes in the amount of ctDNA/MAF in case of suspected progressive disease or relapse after medical imaging 9. specificity and sensitivity of this biomarker 10. costs of medical imaging versus biomarker diagnostic Assessment of safety: Not applicable (no study-specific therapeutic intervention planned apart from study related blood withdrawals)
Study Design
- Purpose:
- Prognosis
- Retrospective/prospective:
- No Entry
- Study type:
- Non-interventional
- Longitudinal/cross-sectional:
- No Entry
- Study type non-interventional:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting planned
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- University medical center Klinik für Hämatologie und Onkologie Lübeck
- University medical center Hämatologie, Zelltherapie und Medizinische Onkologie Dresden
- Medical center Helios Klinikum Bad Saarow Bad Saarow
- University medical center Sarkomzentrum UMM Mannheim Mannheim
- University medical center Westdeutsches Tumorzentrum Essen Essen
- Medical center Helios Klinikum Berlin: Sarkomzentrum Berlin-Brandenburg Berlin
- University medical center SarKUM, Zentrum für Knochen- und Weichteiltumore München
- University medical center Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation Hannover
- University medical center UniversitätsKrebszentrum Göttingen, Göttingen
Recruitment period and number of participants
- Planned study start date:
- 2022-05-01
- Actual study start date:
- No Entry
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 100
- Final Sample Size:
- No Entry
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
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum Schleswig-Holstein Klinik für Hämatologie und Onkologie Campus LübeckProf. Dr. med. Nikolas von BubnoffRatzeburger Allee 16023538 LübeckGermany
- Telephone:
- +49 (0) 451-500-44151
- Fax:
- +49 (0) 451-500-44154
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uksh.de/haemonk-luebeck/
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum Schleswig-Holstein Campus LübeckProf. Dr. med. Nikolas von BubnoffRatzeburger Allee 16023538 LübeckGermany
- Telephone:
- +49-451-500-44151
- Fax:
- +49-451-500 44154
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://intranet.uksh.de/Haemonk_Luebeck/
Contact for Public Queries
- Address:
- Universitätsklinikum Schleswig-Holstein Campus LübeckEmilia PrießRatzeburger Allee 16023538 LübeckGermany
- Telephone:
- +49-451-500-44355
- Fax:
- +49-451-500-44358
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://intranet.uksh.de/Haemonk_Luebeck/
Principal Investigator
- Address:
- Universitätsklinikum Schleswig-Holstein Campus LübeckProf. Dr. med. Nikolas von BubnoffRatzeburger Allee 16023538 LübeckGermany
- Telephone:
- +49-451-500-44151
- Fax:
- +49-451-500 44154
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://intranet.uksh.de/Haemonk_Luebeck/
Sources of Monetary or Material Support
Private sponsorship (foundations, study societies, etc.)
- Address:
- Hector StiftungAm Schloßberg 269469 WeinheimGermany
- Telephone:
- +49 (0) 6201 7108410
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.hector-stiftung.de/startseite
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission der Med. Fakultät der Universität zu LübeckRatzeburger Allee 16023538 LübeckGermany
- Telephone:
- +49-451-5004639
- Fax:
- +49-451-5003026
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2020-05-18
- Ethics committee number:
- 20-196
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2020-09-23
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry