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

NCT ID: NCT03092128

Last Updated: 2018-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2020-06-30

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.

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.

Conditions

Gastrointestinal Stromal Tumors; Germline Mutation; Somatic Mutation; Plasma Concentration

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Xueding Wang

OTHER

Sponsor Role: lead

Responsible Party

Xueding Wang

Institute of Clinical Pharmacology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Min Huang, Professor

Role: STUDY_CHAIR

Institute of Clinical Pharmacology, SunYat-senU

Locations

Institute of Clinical Pharmacology, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Zhuang, Ph.D

Role: CONTACT

zhuangw@mail2.sysu.edu.cn

86-13427526343

Min Huang, Professor

Role: CONTACT

Huangmin@mail.sysu.edu.cn

86-020-39943027

Facility Contacts

Wei Zhuang, Ph. D

Role: primary

zhuangw@mail2.sysu.edu.cn

86-13427526343

Min Huang, Professor

Role: backup

huangmin@mail.sysu.edu.cn

+86 020 87331409 ext. 101

References

Angelini S, Ravegnini G, Fletcher JA, Maffei F, Hrelia P. Clinical relevance of pharmacogenetics in gastrointestinal stromal tumor treatment in the era of personalized therapy. Pharmacogenomics. 2013 Jun;14(8):941-56. doi: 10.2217/pgs.13.63.

Reference Type: BACKGROUND

PMID: 23746188 (View on PubMed)

Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009 Jul 1;27(19):3141-7. doi: 10.1200/JCO.2008.20.4818. Epub 2009 May 18.

Reference Type: BACKGROUND

PMID: 19451435 (View on PubMed)

Bouchet S, Poulette S, Titier K, Moore N, Lassalle R, Abouelfath A, Italiano A, Chevreau C, Bompas E, Collard O, Duffaud F, Rios M, Cupissol D, Adenis A, Ray-Coquard I, Bouche O, Le Cesne A, Bui B, Blay JY, Molimard M. Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting. Eur J Cancer. 2016 Apr;57:31-8. doi: 10.1016/j.ejca.2015.12.029. Epub 2016 Feb 4.

Reference Type: BACKGROUND

PMID: 26851399 (View on PubMed)

Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumour. Lancet. 2013 Sep 14;382(9896):973-83. doi: 10.1016/S0140-6736(13)60106-3. Epub 2013 Apr 24.

Reference Type: BACKGROUND

PMID: 23623056 (View on PubMed)

Other Identifiers

SYSUCC20141021007

Identifier Type: -

Identifier Source: org_study_id