A Retrospective Pharmacogenomics Research of EGFR-TKIs,Gefitinib and Erlotinib, in NSCLC Patients Treatment

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT01994057

Collaborator

(none)

1,000

Enrollment

Location

111

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

For patients of advanced NSCLC (non small cell lung cancer) , Individualized cancer therapy has been widely accepted since the success of crizotinib administration based on EML4-ALK fusion gene detection and gefitinib and erlotinib administration based on EGFR-TKIs 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 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 , trough concentration and EGFR-TKI drug effect, the association between ADME-associated SNP ,trough concentration and EGFR-TKI adverse effect .Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer (NSCLC) EGFR-TKI Resistant Mutation EGFR-TKI Sensitizing Mutation Germline Mutations Somatic Mutation

Detailed Description

The ADME-associated SNPs included are CYP3A4,CYP3A4,CYP1A1,CYP2D6, ABCB1,ABCG2 and so on .The somatic mutations included are EGFR ,K-RAS ,ALK and so on

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

Official Title:

Retrospective Study Based on Somatic Mutations, Genetic Polymorphisms and Metabolomics Related to Individual Variations of Drug Effect and Adverse Drug Reaction of EGFR-TKIs,Gefitinib and Erlotinib in Non-small Cell Lung Cancer Treatment.

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
sensitive group; resistant group sensitive patients were defined as patients reached CR or PR after first month administration,SD after first three months administration. resistant patients were defined as patients reached PD after first month administration and first three months administration

Outcome Measures

Primary Outcome Measures

Progression free survival [The length of time from either the date of diagnosis to that patients diagnosed with the disease are still alive]
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

Number of patients with objective response and adverse events [one month, three 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 NCI-CTC .

Other Outcome Measures

Number of patients with ADR [one month, three month]
Such as rash

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The main patient entry criteria included: age≥ 18 years ; histologically and cytologically proved NSCLC; Eastern cooperative oncology group performance status (ECOG PS)≤2; adequate hematological , renal, and hepatic functions. Exclusion Criteria:

uncontrolled systemic disease ,any evidence of clinically active interstitial lung diseases, 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.