A Retrospective Pharmacokinetics and Pharmacogenomics Research of Imatinib in Gastrointestinal Stromal Tumor Treatment

September 11, 2018 updated by: Xueding Wang

Retrospective Study Based on Pharmacokinetics, Somatic Mutations and Genetic Polymorphisms Related to Individual Variations of Drug Effect and Adverse Drug Reaction of Imatinib in Gastrointestinal Stromal Tumor Treatment.

For patients of GIST (Gastrointestinal Stromal Tumor), Imatinib has been widely used in GIST with KIT or PDGFRA sensitive mutations. From clinical points of view, individual differences often occur between different patients, leading diverse effect in ADR and drug effect. Meanwhile, the drug effect and adverse drug reaction was significantly influenced by the pharmacokinetic factors and pharmacodynamic and other factors. In this research, we try to establish a more sensitive method to detect sensitive mutations in plasma and discover the correlation between somatic and germline mutations, plasma trough concentration and drug effect, the association between ADME-associated SNP, Target/Receptor/Pathway-associated SNP, trough concentration and TKI adverse effect. Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.

Study Overview

Status

Unknown

Conditions

Detailed Description

The plasma concentration of Imatinib were established. The ADME-associated SNPs included are CYP3A4, CYP3A4, CYP1A1, CYP2C9, CYP2C19, ABCB1, ABCG2, ABCC4, SLC22A1, SLCO1B3 and so on. The Target/Receptor/Pathway-associated SNP s included KIT, PDGFRA, PDGFRB, FLT1, FLT3, MAPK1, SHC1, CCL5, CXCL14 and so on. The somatic mutations included are KIT, PDGFRA, BRAF and so on.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Institute of Clinical Pharmacology, Sun Yat-sen University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.

Description

Inclusion Criteria:

  • The main patient entry criteria included: age≥ 18 years; histologically and cytologically proved GIST; Eastern cooperative oncology group performance status (ECOGPS)≤2; adequate hematological,renal,and hepatic functions.

Exclusion Criteria:

  • uncontrolled systemic disease,and other chemotherapy at the time of inclusion. The protocol was approved by the Ethical Committee of Cancer Center of Sun Yat-Sen University (CCSU), and written informed consent was obtained form each patient.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
sensitive group; non-sensitive group
sensitive patients were defined as patients reached CR or PR after first month administration,SD after first three months administration. non-sensitive patients were defined as patients reached PD after first month administration and first three months administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: The time from the date of randomisation (baseline) to the date of objective tumour progression，and expected average of 36 months.
Excluding clinical deterioration without evidence of objective progression according to the Response Evaluation Criteria In Solid Tumors (RECIST), or death from any cause.
The time from the date of randomisation (baseline) to the date of objective tumour progression，and expected average of 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with objective response and adverse events
Time Frame: one month, three month, 12 month
Objective responses (complete response plus partial response) and disease control (objective response plus stable disease≥6 weeks) were established according to RECIST.And adverse events was established according to CTCAE.
one month, three month, 12 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xueding Wang

Collaborators

Sun Yat-sen University

Investigators

  • Study Chair: Min Huang, Professor, Institute of Clinical Pharmacology, SunYat-senU

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2014

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

June 1, 2020

Study Registration Dates

First Submitted

March 21, 2017

First Submitted That Met QC Criteria

March 21, 2017

First Posted (Actual)

March 27, 2017

Study Record Updates

Last Update Posted (Actual)

September 13, 2018

Last Update Submitted That Met QC Criteria

September 11, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SYSUCC20141021007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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