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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03092128
Recruitment Status : Recruiting
First Posted : March 27, 2017
Last Update Posted : September 13, 2018
Sun Yat-sen University
Information provided by (Responsible Party):
Xueding Wang, Sun Yat-sen University

Brief Summary:
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.

Condition or disease
Gastrointestinal Stromal Tumors Germline Mutation Somatic Mutation Plasma Concentration

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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: 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.
Actual Study Start Date : June 2014
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Biospecimen Retention:   Samples With DNA
  1. FFPE samples of tissue needle biopsy were used for KIT and PDGFRA mutation detection.
  2. EDTA-whole blood was centrifuged at 4000rpm*10min,plasma was separated within four hours for somatic mutation detection.The remaining samples were used for germline mutation detection. All the blood samples were frozen in -80℃ until analysis.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.

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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT03092128

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Contact: Wei Zhuang, Ph.D 86-13427526343
Contact: Min Huang, Professor 86-020-39943027

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China, Guangdong
Institute of Clinical Pharmacology, Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Wei Zhuang, Ph. D    86-13427526343   
Contact: Min Huang, Professor    +86 020 87331409 ext 101   
Sponsors and Collaborators
Xueding Wang
Sun Yat-sen University
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Study Chair: Min Huang, Professor Institute of Clinical Pharmacology, SunYat-senU

Additional Information:
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Responsible Party: Xueding Wang, Institute of Clinical Pharmacology, Sun Yat-sen University Identifier: NCT03092128     History of Changes
Other Study ID Numbers: SYSUCC20141021007
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xueding Wang, Sun Yat-sen University:
Gastrointestinal stromal tumor (GIST)
Precision medicine
Somatic and germ-line mutations

Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action