Erlotinib as Neoadjuvant Treatment in Patients With Stage ⅢA N2 NSCLC With Activating EGFR Mutation.

Study Overview
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Brief Summary
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This is a single arm, one center, phaseⅡ study evaluating efficacy and safety of erlotinib as neoadjuvent treatment in patients with EBUS confirmed stage ⅢA N2 NSCLC with activating EGFR mutation in exon 19 or 21.

Detailed Description
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Screening phase: Patients clinically diagnosed as stage ⅢA N2 lung caner by CT technique will be pathologically proven as NSCLC with N2 by EBUS. The pathology specimen will be detected EGFR mutation by DNA sequencing. The patients with EGFR mutation in exon 19 or 21 will be enrolled in this study. Neoadjuvant treatment phase: Patient will receive erlotinib 150mg/day. Treatment will be scheduled to continue for a total of 8 weeks or disease progression or unacceptable toxicities. Surgery treatment phase: Tumor response will be evaluated with CT scan after 8 weeks of induction treatment. The patients with responsive disease considered to be technique resectable will undergo resection. Post-surgery phase: It is the discretion of the investigator whether the patient is a candidate for post-operative treatment which is considered to be in the best interest of the patients. It is recommended that patients with positive margins or residual tumor after surgery should receive radiation therapy. Patients after surgery will receive long-term follow-up including chest CT scan every 3 months for up to 2 years.

Official Title
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A Single Arm, One Center, Phase Ⅱ Study of Erlotinib as Neoadjuvent Treatment in Patients With Endobronchial Ultrasound Confirmed Stage ⅢA N2 NSCLC With EGFR Mutation in Exon 19 or 21

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided. Males or females aged ≥18 years. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications. Stage IIIA N2 NSCLC according to the pathological evidence of endobronchial ultrasound(EBUS). The biopsy specimen shows EGFR mutation in exon 19 or 21 by DNA sequencing. Measurable disease must be characterized according to RECIST criteria: measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20cm with conventional techniques (PE, CT, XR, MRI) or as ≥ 10cm with spiral scan. ECOG performance status 0-1. Life expectancy ≥12 weeks. Female subjects should not be pregnant or breast-feeding. Exclusion Criteria: The biopsy specimen shows EGFR wildtype in exon 19 or 21 by DNA sequencing. 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). Known hypersensitivity to Tarceva or any of its recipients. Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the subject at high risk for treatment-related complications. Sexually active males and females(of childbearing potential) unwilling to practice contraception during the study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Single-arm | Drug: erlotinib<br>* erlotinib 150mg/d continuously for 56 days<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radical resection rate | To evaluate radical resection rate of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | operation after effective neoadjuvant treatment of tarceva for 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Remission | To evaluate Pathological Complete Remission (pCR) rate of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | operation after effective neoadjuvant treatment of tarceva for 56 days | 
| Objective Response Rate | To evaluate Objective Response Rate (ORR) of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | Objective Response Rate measured by RECIST criteria in ITT population treated by erlotinib | 
| disease free survival | To evaluate disease free survival(DFS) of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | From surgery to disease relapse or death | 
| overall survival | To evaluate overall survival(OS) of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | From study treatment to death due to any cause | 
| quality of life | To evaluate quality of life(QOL) of Tarceva as neoadjuvant treatment in patient with EBUS confirmed stage ⅢA N2 NSCLC with EGFR mutation in exon 19 or 21. | During study treatment period | 
| safety profile | To evaluate the safety profile using NCI CTC AE(version 4.0) | For all the patient accepted study treatment | 
| explorative biomarkers | To evalutate the relationship between biomarker and Tarceva neoadjuvent treatment efficacy (TBD). | During study conduction period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant treatment