Gefitinib Versus Vinorelbine/Platinum as Adjuvant Treatment in Stage II-IIIA(N1-N2) NSCLC With EGFR Mutation

NCT ID: NCT01405079

Last Updated: 2020-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-19

Study Completion Date

2020-12-31

Brief Summary

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Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese Non-small Cell Lung Cancer(NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.

Detailed Description

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Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and vinorelbine combination is the standard of care in adjuvant setting. The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall survival(OS) advantage in overall population. While the median gefitinib treatment time is only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis. The study closed prematurely in 2005.

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.

Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gefitinib

Gefitinib 250 mg/day oral daily

Group Type EXPERIMENTAL

Gefitinib

Intervention Type DRUG

Gefitinib 250 mg/day oral daily

Vinorelbine+Cisplatin

Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles

Group Type ACTIVE_COMPARATOR

Vinorelbine+Cisplatin

Intervention Type DRUG

Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles

Interventions

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Gefitinib

Gefitinib 250 mg/day oral daily

Intervention Type DRUG

Vinorelbine+Cisplatin

Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles

Intervention Type DRUG

Other Intervention Names

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Iressa

Eligibility Criteria

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Inclusion Criteria

* Written informed consent provided.
* Males or females aged ≥18 years, \< 75 years.
* Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
* Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation.
* Patient who can start the investigational therapy within 3-6 weeks after the complete resection
* ECOG performance status 0-1.
* Life expectancy ≥12 weeks.
* Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
* Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
* Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
* Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria

* Known severe hypersensitivity to gefitinib or any of the excipients of this product.
* Known severe hypersensitivity to pre-medications required for treatment with cisplatin / vinorelbine doublet chemotherapy.
* Inability to comply with protocol or study procedures.
* A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
* A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
* Interstitial pneumonia.
* Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
* Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
* Patients with prior radiotherapy
* History of another malignancy in the last 5 years with the exception of the following:Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
* Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
* Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
* Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.
* Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
* Patients who harbouring exon 20 T790M mutation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guangdong Provincial People's Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role collaborator

Jilin Provincial Tumor Hospital

OTHER

Sponsor Role collaborator

Liaoning Cancer Hospital & Institute

OTHER

Sponsor Role collaborator

First Hospital of China Medical University

OTHER

Sponsor Role collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role collaborator

Peking University People's Hospital

OTHER

Sponsor Role collaborator

Beijing Chest Hospital

OTHER

Sponsor Role collaborator

309th Hospital of Chinese People's Liberation Army

OTHER

Sponsor Role collaborator

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role collaborator

Peking University First Hospital

OTHER

Sponsor Role collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role collaborator

Jiangsu Cancer Institute & Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role collaborator

Fudan University

OTHER

Sponsor Role collaborator

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role collaborator

Zhejiang University

OTHER

Sponsor Role collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role collaborator

Tongji Hospital

OTHER

Sponsor Role collaborator

West China Hospital

OTHER

Sponsor Role collaborator

Tang-Du Hospital

OTHER

Sponsor Role collaborator

Guangdong Association of Clinical Trials

OTHER

Sponsor Role lead

Responsible Party

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Yi-Long Wu

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yi-Long WU, MD

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Xue-Ning YANG, MD

Role: STUDY_CHAIR

Guangdong Provincial People's Hospital

Wen-Zhao ZHONG, MD

Role: STUDY_DIRECTOR

Guangdong Provincial People's Hospital

Locations

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Guangdong General Hospital

Guangzhou, , China

Site Status

Countries

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China

References

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Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, D'Angelo SP, Kris MG, Shen R, Zheng J, Azzoli CG. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol. 2011 Mar;6(3):569-75. doi: 10.1097/JTO.0b013e318202bffe.

Reference Type BACKGROUND
PMID: 21150674 (View on PubMed)

Occhipinti M, Imbimbo M, Ferrara R, Simeon V, Fiscon G, Marchal C, Skoetz N, Viscardi G. Adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of people with resected stage I to III non-small-cell lung cancer and EGFR mutation. Cochrane Database Syst Rev. 2025 May 27;5(5):CD015140. doi: 10.1002/14651858.CD015140.pub2.

Reference Type DERIVED
PMID: 40421698 (View on PubMed)

Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. doi: 10.1200/JCO.20.01820. Epub 2020 Dec 17.

Reference Type DERIVED
PMID: 33332190 (View on PubMed)

Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. doi: 10.1016/S1470-2045(17)30729-5. Epub 2017 Nov 21.

Reference Type DERIVED
PMID: 29174310 (View on PubMed)

Other Identifiers

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CTONG 1104

Identifier Type: OTHER

Identifier Source: secondary_id

CTONG 1104

Identifier Type: -

Identifier Source: org_study_id

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