Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma

Study Overview
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Brief Summary
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Icotinib is a first-generation inhibitor of EGFR-tyrosine kinase inhibitor in patients with non-small-cell lung cancer (NSCLC). Here we will evaluate neoadjuvant Icotinib with chemotherapy prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary endpoint is centrally assessed major pathological response at the time of resection. Secondary endpoints include pathological complete response, objective response rate, R0 resection rate at the time of resection, disease-free survival, and overall survival. Safety and tolerability will also be assessed.

Official Title
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Neoadjuvant Icotinib With Chemotherapy for Resectable Stage II-IIIB N2 EGFR Mutation-positive Lung Adenocarcinoma: A Phase II Study

Conditions
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NSCLC, EGF-R Positive Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Icotinib
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent Male or female, aged ≥18 years and ≤75 years Histologically or cytologically documented lung adenocarcinoma with completely resectable disease (Stage II-IIIB N2, according to the 8th edition of the IASLC Staging Manual in Thoracic Oncology) Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by an MDT evaluation A tumor which harbors either Ex19del or L858R EGFR-TKI-sensitizing mutations, either alone ECOG PS 0/1 at enrollment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing Adequate organ and marrow function as defined by: Hemoglobin: ≥9.0 g/dL Absolute neutrophil count: ≥1.5 × 109/l Platelet count: ≥100 × 109/l Serum bilirubin: ≤1.5 ULN ALT and AST: ≤2.5 × ULN Creatinine clearance: ≥60 ml/min Life expectancy of 6 months prior to randomization Exclusion Criteria: Prior treatment with systemic anti-cancer treatment for NSCLC, EGFR-TKI treatment or pre-operative radiotherapy EGFR-TKI-sensitizing mutations with T790M Mixed small cell and non-small-cell lung cancer histology T4 tumors infiltrating the aorta, esophagus and/or heart Bulky N2 disease Candidates for segmentectomies or wedge resections only Medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD Severe or uncontrolled systemic diseases/active infections, history of allogeneic organ transplantation, history of primary immunodeficiency, history of another primary malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Icotinib+chemotherapy<br>Neoadjuvant chemotherapy (pemetrexed + carboplatin/cisplatin ) will start within 1-3 days from enrollment at 21-day (+/-3 days) intervals (Q3W) prior to surgery. Before surgery a tumor assessment will be done to exclude evidence of progression. Patients with radiographically stable disease or partial response may be considered for operation. Icotinib will be given as a neoadjuvant therapy before surgical resection. The recommended dose of Icotinib is 125mg 1tt(Take 1 tablet 3 times a day) orally. Surgery: Surgery must be done within the 3rd to 4th week (+7 days) from day 21 cycle 2 of neoadjuvant treatment. Adjuvant treatment: Patients receive additional 2 cycles of platinum-based doublet chemotherapy(Researcher decide) on day 1 with intercalated icotinib (D8-15) every 3 weeks, and continued icotinib for 2 years or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity | Drug: Icotinib<br>* 125mg 1tt(Take 1 tablet 3 times a day) orally.<br>* Other names: Conmana;Drug: Cisplatin<br>* 75 mg/m2 (IV，Q3W)<br>Drug: Carboplatin<br>* AUC 5 (IV, Q3W)<br>Drug: Pemetrexed<br>* 500 mg/m2 (IV, Q3W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response(MPR) | Patients with tumors with ≤10% residual viable cancer cells (identified by routine hematoxylin and eosin staining) in the lung primary tumor after neoadjuvant treatment at the time of resection will be considered to have had an MPR. | Up to approximately 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) | Patients with no residual viable tumor cells in any of the specimens (primary tumors, lymph nodes and margins) will be considered to have had a pCR. | Up to approximately 30 months | 
| Objective response rate(ORR) | defined as the sum of the complete response plus partial response divided by the total number of included patients. | Up to approximately 30 months | 
| R0 resection rate | Free resection margins proved microscopically;Systematic nodal dissection in its wider form or, if it is not performed, lobe-specific systematic nodal dissection;There should be no extracapsular extension of tumor in nodes removed separately or those at the margin of the main lung specimen. ;The highest mediastinal node that has been removed must be negative. | Up to approximately 30 months | 
| Disease-free survival(DFS) | DFS will be defined as the time from surgery until the first instance of disease recurrence (local or distant) or death due to any cause, whichever occurs first. | Up to approximately 72 months | 
| Overall survival(OS) | OS will be defined as the time from randomization until death due to any cause. | Up to approximately 72 months | 

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