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

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ClinicalTrials.gov Identifier: NCT01405079

Recruitment Status : Unknown

Verified February 2020 by Yi-Long Wu, Guangdong Association of Clinical Trials.
Recruitment status was: Active, not recruiting

First Posted : July 29, 2011

Last Update Posted : February 18, 2020

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Sponsor:

Collaborators:

Guangdong Provincial People's Hospital

First Affiliated Hospital, Sun Yat-Sen University

Sun Yat-sen University

Jilin Provincial Tumor Hospital

Liaoning Tumor Hospital & Institute

First Hospital of China Medical University

Chinese PLA General Hospital

Peking Union Medical College Hospital

Peking University People's Hospital

Beijing Chest Hospital

309th Hospital of Chinese People's Liberation Army

Peking University Cancer Hospital & Institute

Peking University First Hospital

Tianjin Medical University Cancer Institute and Hospital

The Affiliated Hospital of Qingdao University

Jiangsu Cancer Institute & Hospital

The First Affiliated Hospital of Soochow University

Fudan University

Shanghai Pulmonary Hospital, Shanghai, China

Zhejiang Cancer Hospital

Zhejiang University

Wuhan Union Hospital, China

Tongji Hospital

West China Hospital

Tang-Du Hospital

Information provided by (Responsible Party):

Yi-Long Wu, Guangdong Association of Clinical Trials

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Gefitinib Drug: Vinorelbine+Cisplatin	Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	222 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized, Open-label Trial of Gefitinib Versus Combination of Vinorelbine Plus Platinum as Adjuvant Treatment in Pathological Stage II-IIIA(N1-N2) Non-small Cell Lung Cancer With EGFR Mutation
Actual Study Start Date :	September 19, 2011
Actual Primary Completion Date :	March 2017
Estimated Study Completion Date :	December 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Cisplatin Vinorelbine Vinorelbine tartrate Gefitinib

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gefitinib Gefitinib 250 mg/day oral daily	Drug: Gefitinib Gefitinib 250 mg/day oral daily Other Name: Iressa
Active Comparator: Vinorelbine+Cisplatin Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles	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

Outcome Measures

Primary Outcome Measures :

Disease free survival [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ]
To evaluate the disease free survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for pathological stage II-IIIA(N1-N2) NSCLC with EGFR mutation.Disease free survival (DFS)- defined as the time from randomization to the first documented disease progression or death, whichever occurs first.

Secondary Outcome Measures :

Overall survival [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ]
To evaluate the overall survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for stage II-IIIA(N1-N2) NSCLC with EGFR mutation.
3 yeas DFS rate, 5 years DFS rate, 5 years OS rate [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ]
To compare the randomized treatment arms in terms of 3 yeas DFS rate, 5 years DFS rate, 5 years OS rate.
Number of Participants with Adverse Events [ Time Frame: In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles. ]
The safety and tolerability profile of gefitinib at a 250 mg daily dose relative to that of Chemotherapy.
The Total Score and TOI of FACT-L to Measure Quality of life [ Time Frame: In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles. ]
Quality of life as measured by the total score and Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) questionnaire.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01405079

Locations

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China
Guangdong General Hospital
Guangzhou, China

Sponsors and Collaborators

Guangdong Association of Clinical Trials