NCT02331914

GIST: Assessment of Tumor Mutations and TKI Plasma Exposure

Completed Last updated 13 May 2025

What this trial tests

trial testing Vena puncture for blood collection in Gastro-intestinal Stromal Tumor in 740 participants. Completed in 31 January 2024.

Timeline

8 December 2014

Primary endpoint
31 January 2024

31 January 2024

Quick facts

Lead sponsor	University Medical Center Groningen
Status	Completed
Study type	OBSERVATIONAL
Enrollment	740
Start date	8 December 2014
Primary completion	31 January 2024
Estimated completion	31 January 2024
Sites	5 locations across Netherlands

Drugs / interventions tested

• Vena puncture for blood collection
• Tumor biopsy

Conditions studied

• Gastro-intestinal Stromal Tumor — all drugs for Gastro-intestinal Stromal Tumor →

Sponsor

University Medical Center Groningen

Who can join

Adults 18 to 90, any sex, with Gastro-intestinal Stromal Tumor. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Gastrointestinal stromal tumors (GISTs) belong to the sarcoma group and are characterized by oncogenic mutations in the c-KIT, PDGFRA, BRAF and NF-1 genes that drive tumor growth. Since tyrosine kinase inhibitors (TKIs) have become available, the median survival of GIST patients increased from 9 months to over 5 years. Consequently, this rare disease has become a role model for other targeted therapies. However, response to TKIs is extremely heterogeneous: \~15% of the patients experience no benefit from imatinib, whereas \~17% of the patients enjoy stable disease for over 9 years. Treatment failure due to primary and secondary resistance is caused in part by mutations in oncogenic genes that cause change in drug sensitivity. A new technique, using circulating tumor DNA, has enabled us to assess mutations in a simple blood sample obtained from patients on treatment, and thus detect new mutations early in the course of the disease. Also, differences in pharmacokinetic drug behavior add to the observed heterogeneity, and may cause resistance due to drug underexposure and thereby proliferation of the least sensitive tumor cells. This offers the opportunity to optimize and personalize targeted treatment for individual GIST patients by timely treatment adaptation based on early detection of secondary TKIs resistance mutations. Achieving this urgently requires data on daily clinical practice, including prospective serial mutation analysis and serial drug plasma concentration measurement. At a fundamental level this will also help to unravel the driving factors behind primary and secondary TKIs resistance in this model disease.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Optimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib.
   Lankheet NAG, Desar IME, Mulder SF, Burger DM, et al · · 2017 · cited 62× · PMID 28500677 · DOI 10.1111/bcp.13327
2. Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients.
   Leest PV, Boonstra PA, Elst AT, Kempen LCV, et al · · 2020 · cited 45× · PMID 32414097 · DOI 10.3390/cancers12051222
3. Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?
   Polivka J, Pesta M, Janku F. · · 2015 · cited 44× · PMID 26559503 · DOI 10.1586/14737159.2015.1110021
4. A single digital droplet PCR assay to detect multiple <i>KIT</i> exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors.
   Boonstra PA, Ter Elst A, Tibbesma M, Bosman LJ, et al · · 2018 · cited 28× · PMID 29568401 · DOI 10.18632/oncotarget.24493
5. Diagnosis and Treatment Monitoring of a Patient with Gastrointestinal Stromal Tumor by Next-Generation Sequencing and Droplet Digital Polymerase Chain Reaction Assay of a PDGFRA Mutation in Plasma-Derived Cell-Free Tumor DNA.
   Boonstra PA, Ter Elst A, Tibbesma M, Gietema JA, et al · · 2019 · cited 3× · PMID 30670599 · DOI 10.1634/theoncologist.2018-0460
6. Levels of circulating tumor DNA correlate with tumor volume in gastro-intestinal stromal tumors: an exploratory long-term follow-up study.
   Bleckman RF, Haag CMSC, Rifaela N, Beukema G, et al · · 2024 · cited 2× · PMID 38790141 · DOI 10.1002/1878-0261.13644
7. Measuring Tumour Imatinib Concentrations in Gastrointestinal Stromal Tumours: Relevant or Redundant?
   Giraud EL, de Jong LAW, van den Hombergh E, Kaal SEJ, et al · · 2023 · PMID 37296838 · DOI 10.3390/cancers15112875