Neoadjuvant Erlotinib for Operable Stage II or IIIA NSCLC With EGFR Mutations

Study Overview
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Brief Summary
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This study examines preoperative Erlotinib in patients with operable stage II and IIIA Non-small-cell lung cancer (NSCLC) harboring EGFR mutations.

Detailed Description
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Lung cancer remains the most common cause of cancer-related death in the world. Non-small-cell lung cancer (NSCLC) is the most common type, and it accounts for 85% of cases. Unfortunately, the majority of patients with NSCLC have metastatic disease at diagnosis. However, even patients with resectable disease have poor survival. The need to improve survival rates in these patients prompted research exploring the role of systemic therapy in operable NSCLC. In the 1990s, several clinical trials of preoperative chemotherapy (also known as induction chemotherapy) followed by surgery or radiation in patients with locally advanced NSCLC showed improvements in survival. Erlotinib is an orally administered tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR). The presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors. Recently three randomized phase III trials showed that first-line use of EGFR-TKIs in patients with EGFR mutant NSCLC significantly improved response rate and progression-free survival (PFS) compared to platinum-based chemotherapy. These findings prompted this phase II trial of preoperative Erlotinib in patients with operable stage II and IIIA NSCLC harboring EGFR mutations.

Official Title
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A Phase II Study of Neo-adjuvant Erlotinib for Operable Stage IIB or IIIA Non-small Cell Lunc Cancer With Epidermal Growth Factor Receptor Activation Mutations

Conditions
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NSCLC Stage II, NSCLC, Stage IIIA

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed stage II & IIIA non-small cell lung cancer EGFR exon 19 or 21 mutations Age ≥ 18 years and ECOG performance 0 1 Has measurable lesion by RECIST 1.1 No previous chemotherapy or radiation therapy Adequate organ function by following; ANC ≥1,500/uL, hemoglobin ≥9.0g/dL, platelet ≥100,000/uL, PaO2 ≥ 60 mmHg, Serum Cr < 1 x UNL or creatinine clearance > 60 ml/min, Serum bilirubin < 1 x UNL, AST (SGOT) and ALT (SGPT) < 2.5 x UNL, alkaline phosphatase < 5 x UNL Written informed consent form Exclusion Criteria: Previous chemotherapy or radiation therapy Previous history of malignancy within 5 years from study entry except treated non-melanomatous skin cancer or uterine cervical cancer in situ Known allergic history of erlotinib Interstitial lung disease or fibrosis on chest radiogram Active infection, uncontrolled systemic disease (cardiopulmonary insufficiency, fatal arrhythmias, hepatitis) Pregnant or nursing women

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: Study arm<br>Neo-adjuvant Erlotinib treatment arm. | Drug: Erlotinib<br>* Neo-adjuvant Erlotinib treatment during maximum 8 weeks.<br>* Other names: treatment arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free survival | Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or to the date of death, whichever occurs first. | every 8 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria 1.1 | every 4 weeks | 
| Overall Survival Rate | Survival time will be calculated from the date of study treatment start to the date of death.( or date last seen ) | every 3months, until death | 
| Toxicity profile | Safety will be evaluated by the frequency, severity, and relationship of adverse event graded by NCI Common Toxicity Criteria version 4.0 that occur during the treatment and follow up periods. | Every 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, EGFR mutation