Induction Erlotinib Therapy in Stage III A (N2) Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the value of induction Erlotinib therapy before thoracotomy or radiotherapy in ⅢA-N2 (confirmed by mediastinoscopy or PET) non-small cell lung cancer (NSCLC) selected by epidermal growth factor receptor (EGFR) gene analysis and initial to explore a new treatment strategy for ⅢA-N2 NSCLC.

Detailed Description
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Stage IIIA non-small-cell lung cancer (NSCLC) is seen in a relatively heterogeneous group of patients with ipsilateral mediastinal (N2) lymph node involvement. The relative roles of different treatment modalities are not clear. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may result in dramatic responses in patients with pulmonary adenocarcinoma carrying EGFR activating mutations. In case reports, the efficacy of perioperative EGFR-TKI therapy in patients with locally advanced NSCLC harboring EGFR gene mutations was satisfactory. Although no prospective data support the use of EGFR-TKIs as induction therapy in stage IIIA-N2 NSCLC, their low toxicity profile and the possibility of a rapid tumor response suggests that prospective trials are required. Therefore, this study evaluated the value of induction erlotinib therapy in IIIA-N2 NSCLC selected by EGFR gene analysis and explored a new treatment strategy for this subset. Erlotinib specifically targets the EGFR TK domain, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.

Official Title
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Phase Ⅱ Study of Induction Erlotinib Therapy in Stage III A(N2) Non-small Cell Lung Cancer Proceeding to Mediastinoscopy/PET and Thoracotomy/Radiotherapy

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: neoadjuvant erlotinib therapy
* Drug: neoadjuvant gemcitabine/carboplatin therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Histological or cytological documented Resectable NSCLC of stage IIIA-N2 confirmed by mediastinoscopy or PET Naive therapy NSCLC Candidates should be tolerated with induction therapy and thoracotomy with ECOG performance status 0-2, adequate haematological and Hepatic- renal function and qualified lung function Enough tissue samples to perform gene analysis Exclusion Criteria: Small cell lung cancer Pregnant or breast-feeding women Any unstable systemic disease Patients with exposure to investigational drug therapy or other concurrent anticancer therapy outside of this trial

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Erlotinib targeted NSCLC population based on EGFR gene analysis(EGFR gene status: activating mutation) | Drug: neoadjuvant erlotinib therapy<br>* 150mg erlotinib taken once daily and continued uninterrupted for 42 days before evaluation/thoracotomy/radiotherapy.<br>* Other names: tarceva;|
| Active Comparator: B<br>Non-erlotinib targeted NSCLC population based on EGFR gene analysis | Drug: neoadjuvant gemcitabine/carboplatin therapy<br>* 3 cycles of neoadjuvant gemcitabine(1250mg/m2,d1,d8)/carboplatin(AUC=5,day1) chemotherapy before evaluation/thoracotomy/radiotherapy.<br>* Other names: gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Neoadjuvant Erlotinib Therapy |  | a week after completion of the induction erlotinib therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival |  | every 3 months | 
| overall survival |  | every 3 months | 
| complete resection rate |  | 7 days after thoractomy | 
| Toxicity of Neoadjuvant Erlotinib Therapy and postoperative complications |  | one months after thoractomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Non-Small-Cell Lung, Genes, erbB-1, tyrosine kinase inhibitor, Neoadjuvant Therapy