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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01994057
• Other study ID #: 2012ZX09506001-004 (2)
• Secondary ID: (2)
• Status: Recruiting
• Start date: September 2012
• Est. completion date: December 2026

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: shaoxing guan, PHD
• Phone: +86 13129351756
• Email: guanshx6[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR-TKI Resistant Mutation
• EGFR-TKI Sensitizing Mutation
• Germline Mutations
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)
• Somatic Mutation

Locations

Country	Name	City	State
China	Cancer Center, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (6)

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. Erratum In: J Clin Oncol. 2004 Dec 1;22(23):4863. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Zhang X, Hayashi N, Wang M; INFORM investigators. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol. 2012 May;13(5):466-75. doi: 10.1016/S1470-2045(12)70117-1. Epub 2012 Apr 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with ADR	Such as rash	one month, three month
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 length of time from either the date of diagnosis to that patients diagnosed with the disease are still alive
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 NCI-CTC .	one month, three month

External Links

•   department of medical oncology ,Cancer Center ,Sun Yat-sen University
•   school of pharmaceutical sciences ,sun yat-sen university