Combination of Chemotherapy and Gefitinib as First-line Treatment

Study Overview
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Brief Summary
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The results of fastact2 show that chemotherapy plus erlotinib significantly prolonged PFS and OS of patients with NSCLC. However, outcome of the combination therapy are similar to those reported in several trials of single-agent EGFR TKIs. So which is the optimal first-line treatment for patients who harbored a sensitive EGFR mutation? The investigators need a head-to-head study to reply.

Official Title
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Combination of Chemotherapy and Gefitinib as First-line Treatment of Patients With Advanced Lung Adenocarcinoma and Sensitive EGFR Mutations: a Randomised Controlled Trial

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed plus carboplatin
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age >=18 years Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic Stage IV Non-Small Cell Lung Cancer (NSCLC) A cytologic diagnosis is acceptable (i.e., FNA or pleural fluid cytology) Measurable or non-measurable disease Able to comply with study and follow-up procedures Exclusion Criteria: Evidence of small cell, carcinoid, or mixed small cell/non-small cell histology Malignancies within 3 years except for adequately treated carcinoma in situ of -the cervix or basal or squamous cell skin cancer Symptomatic or untreated brain metastases Prior systemic chemotherapy for NSCLC Unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or serious cardiac arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible) History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, or prior surgical procedures affecting absorption Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy group(B)<br>pemetrexed plus carboplatin pemetrexed (500 mg/m(2) on day 1) plus carboplatin (AUC 5 on day 1) every 4 weeks for up to six cycles, then continued to receive pemetrexed(500 mg/m(2) on day 1) alone every 4 weeks | Drug: pemetrexed plus carboplatin<br> <br> * Other names: Alimita plus carboplatin;|
| Experimental: combination therapy group(A)<br>pemetrexed (500 mg/m(2) on day 1) plus carboplatin (AUC 5 on day 1) combined with gefitinib (250 mg/day on days 5-21) and repeated every 4 weeks for up to six cycles,then continued to receive pemetrexed combined with gefitinib every 4 weeks. | Drug: pemetrexed plus carboplatin<br> <br> * Other names: Alimita plus carboplatin;Drug: gefitinib<br> <br> * Other names: Iressa;|
| Experimental: gefitinib group (group C)<br>received gefitinib( 250 mg/day)alone. All therapies of 3 groups were continued until progression or unacceptable toxicity or death | Drug: gefitinib<br> <br> * Other names: Iressa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 6-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 2 years | 
| to evaluate the safety profile between three groups | Toxicity will be graded according to NCI CTCAE, version 4.0. The analysis of safety/tolerability data will be descriptive; toxicity events will be individually tabulated. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung adenocarcinoma,EGFR mutation, chemotherapy, gefitinib