GIST: Assessment of Tumor Mutations and TKI Plasma Exposure
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|ClinicalTrials.gov Identifier: NCT02331914|
Recruitment Status : Recruiting
First Posted : January 6, 2015
Last Update Posted : May 18, 2022
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|Condition or disease||Intervention/treatment|
|Gastro-intestinal Stromal Tumor||Procedure: Vena puncture for blood collection Procedure: Tumor biopsy|
The treatment of Dutch GIST patients is centralized: almost all patients are referred to one of the five collaborating centers forming the Dutch GIST consortium, UMCG, NKI-AvL, Radboud UMC, Erasmus MC and LUMC. To further optimize treatment for all patients, these centers have implemented a standard-of-care diagnostic and treatment plan that assures collection of homogenous phenotypic and treatment data for the bio-databank. The consortium is supported by and works in close collaboration with the Dutch sarcoma and GIST patient organizations.
A prospective, longitudinal bio-databank will be set up. Data regarding multi-morbidity, drug pharmacokinetics and serial tumor genotypic data will be collected prospectively from all (new) GIST patients during TKI treatment. Our standard-of-care plan includes primary tumor mutation analysis, performed by pathology laboratories on site. At each follow up visit during treatment, blood will be collected to assess TKI plasma exposure and to perform mutation analysis on circulating tumor DNA. All patients will be followed for tumor RECIST 1.1 progression assessed by CT scans and asked to undergo a tumor biopsy at progression to detect secondary resistance mutations.
The development of a model predicting secondary imatinib resistance based on patient phenotype and tumor genotype, will be achieved by analyzing GIST patients with progressive disease on imatinib (index patients; n=30) in our bio-databank. These patients will be matched 1:1 with non-progressive patients treated for the same duration as the index patients. Regarding the index patients, next-generation gene-targeted mutation analysis will be performed on archival tumor material and on a tumor biopsy at progression to identify patient's unique secondary mutations. The mutations that will be studied are: KIT exon 9, exon 11, exon 13, exon 14, exon 17 and exon 18; PDGFRA exon 12, exon 14 and exon 18 and BRAF exon 10 en exon 15.
In-depth analysis regarding mutation analysis in circulating tumor DNA and imatinib drug concentration assessment will be performed for these 60 patients.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|Official Title:||Gastrointestinal Stromal Tumors: Assessment of Mutations in Tumors and in Circulating Tumor DNA and Measurement of TKI Plasma Exposure to Optimize Treatment|
|Actual Study Start Date :||December 8, 2014|
|Estimated Primary Completion Date :||September 2024|
|Estimated Study Completion Date :||September 2024|
Gastro-intestinal stromal tumors
A bio-databank consisting of TKI drug level and serum for analysis of mutations in circulating tumor DNA will be set up. This bio-databank will be used to study whether changes in the amount of the primary KIT mutation is an early predictor of treatment response and/of failure. Moreover, secondary TKI resistant mutations in circulating tumor DNA will be assessed.
To be able to assess those mutations, a tumor biopsy will be performed at the time of radiologic progressive disease. Vena puncture for blood collection will be performed at routine out patient visits.
Procedure: Vena puncture for blood collection
GIST patients will be asked to provide 40ml blood that will be collected in four Na-EDTA 10ml blood collection tubes at every routine outpatient visit.
Procedure: Tumor biopsy
Tumor biopsy after disease progression
- Secondary GIST mutations in circulating tumor DNA of patients with progressive disease on TKI treatment [ Time Frame: 2 years ]To assess whether secondary GIST mutations can be found in circulating tumor DNA of patients with progressive disease on TKI treatment (according to RECIST 1.1 on computer tomography), whereas they are NOT present in the patients that have no progressive disease after the same time of TKI treatment
- Secondary mutations in circulating tumor DNA before progressive disease according RECIST [ Time Frame: 2 years ]To establish whether these secondary mutations can be detected some time (> 3 months) before progressive disease is assessed according to RECIST 1.1 on computer tomography
- Secondary mutations in circulating tumor DNA related to pharmacokinetics of TKI [ Time Frame: 2 years ]To assess whether the occurence of secondary mutations in circulating tumor DNA is related to TKI trough levels
Biospecimen Retention: Samples With DNA
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|Ages Eligible for Study:||18 Years to 90 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Probability Sample|
- Patients diagnosed with a GIST with an indication to be treated with a TKI of whom a histological biopsy before start treatment is available.
- Informed consent is given
- Patients of whom no tumor is available before start of first line TKI
- Patients that refuse a tumor biopsy in case of tumor progression
- Patients in whom it will not be possible to perform a biopsy in case of tumor progression (for example anti-coagulants that cannot be interrupted).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02331914
|Contact: A. K. Reyners, MD, PhD||+31 50 361 email@example.com|
|Antoni van Leeuwenhoek Hospital||Not yet recruiting|
|Contact: N. Steeghs, MD, PhD firstname.lastname@example.org|
|Principal Investigator: N. Steeghs, MD, PhD|
|University Medical Center Groningen||Recruiting|
|Groningen, Netherlands, 9713 GZ|
|Contact: A. K. Reyners, MD, PhD +31 50 361 2821 email@example.com|
|Principal Investigator: A. K. Reyners, MD, PhD|
|Leiden University Medical Center||Not yet recruiting|
|Contact: A. J. Gelderblom, MD, PhD A.J.Gelderblom@lumc.nl|
|Principal Investigator: A. J. Gelderblom, MD, PhD|
|University Medical Center St. Radboud||Not yet recruiting|
|Contact: W. T. van der Graaf, MD, PhD Winette.vanderGraaf@radboudumc.nl|
|Principal Investigator: W. T. van der Graaf, MD, PhD|
|Erasmus MC||Not yet recruiting|
|Contact: R. H. Mathijssen, MD, PhD firstname.lastname@example.org|
|Principal Investigator: R. H. Mathijssen, MD, PhD|
|Principal Investigator:||A. K. Reyners, MD, PhD||University Medical Center Groningen|
|Responsible Party:||A.K.L. Reyners, Principal investigator, University Medical Center Groningen|
|Other Study ID Numbers:||
|First Posted:||January 6, 2015 Key Record Dates|
|Last Update Posted:||May 18, 2022|
|Last Verified:||May 2022|
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Digestive System Neoplasms
Digestive System Diseases