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GIST: Assessment of Tumor Mutations and TKI Plasma Exposure

NCT02331914 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 740

Last updated 2025-05-13

No results posted yet for this study

Summary

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.

Conditions

  • Gastro-intestinal Stromal Tumor

Interventions

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

Sponsors & Collaborators

  • Dutch Cancer Society

    collaborator OTHER

  • University Medical Center Groningen

    lead OTHER

Principal Investigators

  • A. K. Reyners, MD, PhD · University Medical Center Groningen

Eligibility

Min Age
18 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-12-08
Primary Completion
2024-01-31
Completion
2024-01-31

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02331914 on ClinicalTrials.gov