Erlotinib Versus Vinorelbine/Cisplatin as Adjuvant Treatment in Stage IIIA NSCLC Patients With EGFR Mutations

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect and safety of erlotinib versus NVB plus cisplatin (NP) as adjuvant treatment in patients with stage IIIA NSCLC after complete resection with EGFR activating mutations and to explore a new treatment strategy for this subset.

Detailed Description
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The LACE meta-analysis identified four cycles of platinum-based program to improve II IIIA stage completely resected NSCLC pts the role of 5-year survival, but its treatment-related life threatening toxicity limits its use. The EGFR tyrosine kinase inhibitor (TKI) may provide a dramatic response in pts with pulmonary adenocarcinoma carrying EGFR activating mutations in the metastatic setting. The aim of this study is to investigate the efficacy and safety of erlotinib versus NVB plus cisplatin (NP) as adjuvant treatment in pts with stage IIIA NSCLC after Complete Resection with EGFR activating mutations and to explore a new treatment strategy for this subset.

Official Title
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A Phase II Trial of Erlotinib Versus Combination of Vinorelbine Plus Cisplatin as Adjuvant Treatment in Stage IIIA Non-small-cell Lung Cancer After Complete Resection With Sensitizing EGFR Mutation in Exon 19 or 21 and Wild-type K-ras

Conditions
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Non-small Cell Lung Cancer Stage IIIA

Intervention / Treatment
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* Drug: Erlotinib
* Drug: vinorelbine/cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided. Males or females aged ≥18 years. Chest CT, brain CT or MRI, ECT, abdominal and double-neck B-, or whole body PET-CT examination in 4 weeks before complete resection. Pathological diagnosed of non-small cell lung cancer. Diagnosed as stage IIIA. In 4 weeks after complete resection pts start to accept the adjuvant therapy in this study, previously did not receive any anti-tumor therapy. EGFR activating mutation in exon 19 or 21 and KARS ECOG performance status 0-1. Life expectancy ≥3 months. Adequate hematological function:Absolute neutrophil count (ANC) ≥1.5 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. Adequate renal function:Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60 ml/min. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications. Patients must be nonpregnant and non-lactating.Patients of childbearing potential must implement an effective method of contraception during the study. All female Patients, except those who are postmenopausal or surgically sterilized, must have a negative pre-study serum or urine pregnancy test. . Exclusion Criteria: 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. Patients with prior radiotherapy. History of another malignancy in the last 5 years with the exception of the following:Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted. Any evidence confirmed tumor recurrence before adjuvant treatment. 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). Any evidence of clinically active interstitial lung disease. Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this. Known human immunodeficiency virus (HIV) infection. Known hypersensitivity to Tarceva or NVB or cisplatin. Pregnancy or breast-feeding women. ECOG performance status ≥ 2. Ingredients mixed with small cell lung cancer patients 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.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib arm<br>In the adjuvant treatment phase, erlotinib 150 mg/day taken orally for 2 years or till disease progression or unacceptable toxicity. | Drug: Erlotinib<br>* In the adjuvant treatment phase, erlotinib 150 mg/day taken orally for 2 years or till disease progression or unacceptable toxicity.<br>* Other names: tarceva;|
| Active Comparator: Chemo arm<br>In the adjuvant treatment phase, patient will receive vinorelbine 25mg/m2 IV on day 1 and day 8, and cisplatin 25mg/m2 on day 1 and day 2 and day 3, of a 3-week schedule for 4 cycles or till disease progression or unacceptable toxicity. | Drug: vinorelbine/cisplatin<br>* In the adjuvant treatment phase, patient will receive vinorelbine 25mg/m2 IV on day 1 and day 8, and cisplatin 25mg/m2 on day 1 and day 2 and day 3, of a 3-week schedule for 4 cycles or till disease progression or unacceptable toxicity.<br>* Other names: NVB/cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | To evaluate Disease-free survival(DFS) of two groups | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | To evaluate the safety profile(Number of Participants with Adverse Events) of two group. | 2 years | 
| Quality of Life (QOL) | To evaluate the Quality of Life (QOL) of two group. | 2 years | 
| overall survival (OS) | To evaluate the overall survival (OS) of two groups | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, EGFR Mutation Positive, complete resection, Erlotinib Versus NVB/Cisplatin as Adjuvant treatment