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

Gastrointestinal Stromal Tumors Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03092128
• Other study ID #: SYSUCC20141021007
• Status: Recruiting
• Start date: June 2014
• Est. completion date: June 2020

Study information

• Verified date: September 2018
• Source: Sun Yat-sen University
• Contact: Wei Zhuang, Ph.D
• Phone: 86-13427526343
• Email: zhuangw[@]mail2.sysu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2020
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
China	Institute of Clinical Pharmacology, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Xueding Wang	Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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, Bouché 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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	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	Number of patients with objective response and adverse events	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

External Links

•   Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center
•   Institute of Clinical Pharmacology, Sun Yat-sen University