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

Xueding Wang

Status: Unknown

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

Study type: Observational

Funder types: Other

Identifiers

NCT03092128

SYSUCC20141021007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 1 patient group

sensitive group; non-sensitive group

Description:

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.