A Retrospective Study of EGFR-TKIs,Gefitinib, Erlotinib and Osimertinib in NSCLC Patients Treatment

NCT ID: NCT01994057

Last Updated: 2023-04-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2026-12-31

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.

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

Conditions

Non-small Cell Lung Cancer (NSCLC); EGFR-TKI Resistant Mutation; EGFR-TKI Sensitizing Mutation; Germline Mutations; Somatic Mutation

Study Design

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

Study Groups

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

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Guan shaoxing, PHD

PHD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Min Huang, Professor

Role: STUDY_CHAIR

school of pharmaceutical sciences , SunYat-senU

Locations

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

shaoxing guan, PHD

Role: CONTACT

guanshx6@mail.sysu.edu.cn

+86 13129351756 ext. +8613129351756

Min Huang, Professor

Role: CONTACT

huangmin@mail.sysu.edu.cn

+86 020 87331409-101

Facility Contacts

Shuang Xin, PHD

Role: primary

xshuang@mail2.sysu.edu.cn

+86 13580479553

shaoxing guan, PHD

Role: backup

guanshx6@mail.sysu.edu.cn

+86 13129351756 ext. 13129351756

References

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Reference Type: BACKGROUND

PMID: 22512843 (View on PubMed)

Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, Lau DH, Crowley JJ, Gandara DR. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008 May 20;26(15):2450-6. doi: 10.1200/JCO.2007.14.4824. Epub 2008 Mar 31.

Reference Type: BACKGROUND

PMID: 18378568 (View on PubMed)

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong RP, Baselga J. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003 Jun 15;21(12):2237-46. doi: 10.1200/JCO.2003.10.038. Epub 2003 May 14.

Reference Type: BACKGROUND

PMID: 12748244 (View on PubMed)

Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. doi: 10.1001/jama.290.16.2149.

Reference Type: BACKGROUND

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Guan S, Chen X, Chen Y, Wan G, Su Q, Liang H, Yang Y, Fang W, Huang Y, Zhao H, Zhuang W, Liu S, Wang F, Feng W, Zhang X, Huang M, Wang X, Zhang L. FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy. Acta Pharm Sin B. 2022 Sep;12(9):3639-3649. doi: 10.1016/j.apsb.2022.02.006. Epub 2022 Feb 15.

Reference Type: BACKGROUND

PMID: 36176901 (View on PubMed)

Guan S, Chen X, Chen Y, Xie W, Liang H, Zhu X, Yang Y, Fang W, Huang Y, Zhao H, Zhuang W, Liu S, Huang M, Wang X, Zhang L. FOXM1 Variant Contributes to Gefitinib Resistance via Activating Wnt/beta-Catenin Signal Pathway in Patients with Non-Small Cell Lung Cancer. Clin Cancer Res. 2022 Sep 1;28(17):3770-3784. doi: 10.1158/1078-0432.CCR-22-0791.

Reference Type: BACKGROUND

PMID: 35695863 (View on PubMed)

Guan S, Chen X, Wei Y, Wang F, Xie W, Chen Y, Liang H, Zhu X, Yang Y, Fang W, Huang Y, Zhao H, Zhang X, Liu S, Zhuang W, Huang M, Wang X, Zhang L. Germline USP36 Mutation Confers Resistance to EGFR-TKIs by Upregulating MLLT3 Expression in Patients with Non-Small Cell Lung Cancer. Clin Cancer Res. 2024 Apr 1;30(7):1382-1396. doi: 10.1158/1078-0432.CCR-23-2357.

Reference Type: DERIVED

PMID: 38261467 (View on PubMed)

Related Links

http://sps.sysu.edu.cn/

school of pharmaceutical sciences ,sun yat-sen university

http://www.sysucc.org.cn/

department of medical oncology ,Cancer Center ,Sun Yat-sen University

Other Identifiers

(2)

Identifier Type: OTHER

Identifier Source: secondary_id

2012ZX09506001-004 (2)

Identifier Type: -

Identifier Source: org_study_id