First-line Icotinib With Concurrent Radiotherapy for NSCLC With EGFR Mutation

Study Overview
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Brief Summary
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Eligible patients are administered with oral icotinib 125mg three times daily for two months, in which responsive patients (partial response and stable disease) are randomized (1: 1: 1) and receive icotinib plus concurrent radiotherapy, or chemotherapy plus concurrent radiotherapy, or icotinib monotherapy.

Detailed Description
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Eligible patients are administered with oral icotinib 125mg three times daily for two months, in which responsive patients (partial response and stable disease) are randomized (1: 1: 1) and receive icotinib plus concurrent radiotherapy, or chemotherapy plus concurrent radiotherapy, or icotinib monotherapy. The primary endpoint is progression-free survival, and the incidence of radiation-induced lung injury.

Official Title
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Phase III Study of Icotinib With Concurrent Radiotherapy as First-line Treatment for Unresectable/Oligometastasis NSCLC With EGFR Activating Mutation: a Prospective, Multicentre, Open-label, Randomised Study

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: icotinib
* Drug: Chemotherapy
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 75 years Pathologically documented NSCLC Unresectable stage III or oligometastasis (less than three metastasis lesions, brain metastasis is not permitted) stage IV confirmed by CT and/or MRI Positive EGFR mutation confirmed by ARMS At least 3-month life expectancy KPS ≥ 70 Adequate hematological values: hemoglobin ≥ 100 g/L, absolute neutrophils count ≥ 1.5 x 109/L, platelets count ≥ 100 x 109/L Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 1.5 x ULN Written informed consent before patient registration and any protocol-related procedures Exclusion Criteria: Previous radiotherapy Received other investigational systemic drugs within 4 weeks prior to study entry Severe or uncontrolled systemic disease Active autoimmune disease, or a documented history of autoimmune/acquired immune disease, or a history of organ transplant Pregnant or lactating, women of childbearing potential, unless using effective contraception as determined by the investigator Any other serious underlying medical (e.g. active uncontrolled infection, active gastric ulcer, uncontrolled seizures), psychological and other condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: icotinib plus radiotherapy<br>Eligible patients are administered with oral icotinib 125mg three times daily for two months, in which responsive patients (partial response and stable disease) are randomized (1: 1: 1) and receive icotinib plus concurrent radiotherapy. | Drug: icotinib<br>* Icotinib is orally administered three times per day.<br>Radiation: Radiotherapy<br>* 5Gy/75.00Gy, 10f/2w for peripheral lung cancer, and 2.4Gy/59.52Gy, 20f/4w for central lung cancer.<br>|
| Active Comparator: icotinib<br>Eligible patients are administered with oral icotinib 125mg three times daily for two months, in which responsive patients (partial response and stable disease) are randomized (1: 1: 1) and receive icotinib monotherapy. | Drug: icotinib<br>* Icotinib is orally administered three times per day.<br>|
| Active Comparator: chemotherapy plus radiotherapy<br>Eligible patients are administered with oral icotinib 125mg three times daily for two months, in which responsive patients (partial response and stable disease) are randomized (1: 1: 1) and receive chemotherapy plus concurrent radiotherapy. | Drug: Chemotherapy<br>* Chemotherapy is given by intravenous administration. Three regimens are available in this study. Regimen 1: etoposide 75mg/m2 d1-5 + cisplatin 75 mg/m2 day1/ day1-2. Regimen 2: docetaxel 75mg/m2 d1 + cisplatin 75 mg/m2 day1/ day1-2. Regimen 3: pemetrexed 500mg/m2 d1 + cisplatin 75 mg/m2 day1/ day1-2<br>Radiation: Radiotherapy<br>* 5Gy/75.00Gy, 10f/2w for peripheral lung cancer, and 2.4Gy/59.52Gy, 20f/4w for central lung cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 2 years | 
| Incidence of radiation injure of the lungs | Measured according to NCI CTCAE v4.0 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 
| Tumor response after icotinib induction |  | 8 weeks | 
| Quality of life | Measured by FACT-L | 2 years |