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

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.

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03092128

Enrollment

200

Registered

2017-03-27

Start date

2014-06-30

Completion date

2020-06-30

Last updated

2018-09-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Gastrointestinal stromal tumor (GIST), Imatinib, Pharmacogenetics, Pharmacokinetics, Precision medicine, Somatic and germ-line mutations

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.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
Progression free survival	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

Measure	Time frame	Description
Number of patients with objective response and adverse events	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.

Countries

China

Contacts

Primary ContactWei Zhuang, Ph.D

zhuangw@mail2.sysu.edu.cn86-13427526343

Backup ContactMin Huang, Professor

Huangmin@mail.sysu.edu.cn86-020-39943027

Outcome results