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

NCT01994057 | Recruiting DMC

• 2 other identifiers: 2012ZX09506001-004 (2)(2)
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Non-small cell lung cancer (NSCLC);; EGFR-TKI;; Pharmacogenetics;; Precision medicine; somatic mutations ,germline mutations;

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of patients with objective response and adverse events

  one month, three month

Other Outcomes (1)

• Number of patients with ADR

  one month, three month

Study Arms (1)

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

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

locally advanced or metastatic NSCLC (non-small cell lung cancer) patients; administrated with gefitinib,erlotinib .

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 22512843 BACKGROUND

• 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.

  PMID: 18378568 BACKGROUND

• 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.

  PMID: 12748244 BACKGROUND

• 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.

  PMID: 14570950 BACKGROUND

• 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.

  PMID: 36176901 BACKGROUND

• 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.

  PMID: 35695863 BACKGROUND

• 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.

  PMID: 38261467 DERIVED

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

1. FFPE samples of tissue needle biopsy were used for EGFR mutation detection. 2. EDTA-whole blood was centrifuged at 4000rpm\*10min,plasma was separated within four hours for somatic mutation detection.The remaining samples were used for germline mutation detection. All the blood samples were frozen in -80℃ until analysis.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Min Huang, Professor

  school of pharmaceutical sciences , SunYat-senU

  STUDY CHAIR

Central Study Contacts

shaoxing guan, PHD

CONTACT

+86 13129351756; guanshx6@mail.sysu.edu.cn

Min Huang, Professor

CONTACT

+86 020 87331409-101; huangmin@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PHD

Study Record Dates

• First Submitted: November 1, 2013
• First Posted: November 25, 2013
• Study Start: September 1, 2012
• Primary Completion: October 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (1)