Clinical Trial of Neoadjuvant Targeted Treatment to NSCLC Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficiency and safety of Gefitinib Neoadjuvant Therapy and Oral Navelbine Carboplatin Neoadjuvant Therapy for Resectable Stage Ⅱ-ⅢA NSCLC patients with EGFR mutation.

Detailed Description
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Lung cancer is the most common cause of cancer mortality in men and women in the world. LACE meta analysis shows that the 5-year survival rate of post-operation chemotherapy group rose by 5.4%, therefore, adjuvant chemotherapy has been the main treatment after surgery according to National Comprehensive Cancer Network (NCCN) Guideline. But patients have poor compliance due to physical condition after surgery. Compared with adjuvant chemotherapy, neoadjuvant therapy has better patient compliance and tolerance.Targeted therapy, with milder side effect compared with chemotherapy, may be a promising choice to treat NSCLC previously. But to date, there is no enough evidence to support the efficacy and safety of neoadjuvant targeted therapy in patients with EGFR mutation.The purpose of this study is to evaluate the efficiency and safety of Gefitinib Neoadjuvant Therapy vs Oral Navelbine Carboplatin Neoadjuvant Therapy for Resectable NSCLC patients harboring EGFR mutation.

Official Title
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Oral Navelbine Carboplatin Versus Gefitinib Neoadjuvant Therapy for Resectable EGFR Mutation Positive Stage Ⅱ-ⅢA NSCLC, Prospective, Randomized, Multicenter, Phase Ⅲ Clinical Trial

Conditions
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2-year Disease-Free Survival

Intervention / Treatment
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* Drug: Oral Navelbine + Carboplatin
* Drug: Gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of non small cell lung cancer, Stage Ⅱ-ⅢA before treatment EGFR Gene mutated ECOG 0-1 liver, kidney and bone marrow are functional healthy，WBC>4.0×109/L，PLT>100×109/L Hb>10g/dL;Cr<1.8mg/dL，bilirubin<1.5mg/dL，GPT<1.5 upper limit of normal No vital systems dysfunction or malnutrition No other malignant diseases in 5 years（except non melanoma or Cervical carcinoma in situ） Have never accepted radiation therapy、overall chemotherapy or biotherapy Know the whole protocol，Voluntary participate and sign a consent form Exclusion Criteria: Tumor has violated the surrounding tissue organs（T4） Preoperative have evidence of distant metastasis including the contralateral mediastinal lymph nodes Arrhythmia need anti-arrhythmic treatment（except for β-blockers or digoxin），Symptomatic coronary artery disease and myocardial ischemia (myocardial infarction) in the past 6 months or more than NYHA class II congestive heart failure Adverse drug control severe hypertension Moderate to severe proteinuria History of HIV infection or activity of chronic hepatitis b or hepatitis c, or other active clinical severe infection Cachexy,organ function decompensation History of chest radiotherapy Not fully control the eye inflammation Epilepsy patients needed treatment（such as Steroids or antiepileptic cure） Interstitial pneumonia Drug abuse and medical, psychological or social conditions may interfere with the patients involved in the research or have an impact on the results of evaluation Known or suspected to study drug allergy or to give any drug allergies associated with this test Any unstable situation or may endanger the patient safety and compliance Fertility and pregnancy or lactation women, and have not been sufficient precautions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Oral Navelbine + Carboplatin<br>Neoadjuvant therapy Patients with EGFR mutation will be recruited and treated with Navelbine + Carboplatin. | Drug: Oral Navelbine + Carboplatin<br>* The patient will be given Navelbine 60 mg/m2, p.o. day 1 and 8 of every cycle (21 days) plus carboplatin AUC 5, i.v. day 1 of every cycle.After 2 cycle we will evaluate their clinical response.Then operable patients will have surgery.<br>* Other names: Carboplat;|
| Experimental: Gefitinib<br>Neoadjuvant therapy Patients with EGFR mutation will be recruited and treated with gefitinib. | Drug: Gefitinib<br>* The patient will be given Gefitinib 250mg,p.o.,q.d. for 8 weeks.After 8 weeks we evaluate their clinical response.Then operable patients will have surgery.<br>* Other names: Iressa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease free survival |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 1 week before surgery | 
| Pathologic complete response |  | Within 1 month after surgery | 
| Side effects |  | 1 week before surgery | 
| Standard uptake value |  | 1 week before surgery | 
| Tumor reduction rate |  | Within 1 month after surgery | 
| Mediastinal lymph nodes clearance |  | Within 1 month after surgery | 
| Postoperative complications |  | Within 1 month after discharge | 
| R0 resection rate |  | Within 1 month after surgery | 
| Postoperative mortality rate |  | Within 1 month after discharge | 
| 5-year overall survival |  | 5 years after surgery |