Icotinib or Whole Brain Irradiation in EGFR-mutant Lung Cancer

Study Overview
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Brief Summary
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EGFR-TKI is good for the patients with EGFR-mutant non-small cell lung cancer.We design this clinical trail to confirm if the efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI )(ICOTINIB) is better than whole brain irradiation for the patient with EGFR-mutant non-small cell lung cancer.

Detailed Description
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no available

Official Title
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Phase III Study of Icotinib Treat the Patient With Brain Metastasis EGFR-mutant Non Small Cell Lung Cancer Comparing With Whole Brain Radiotherapy

Conditions
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Brain Metastasis, Non Small Cell Lung Cancer

Intervention / Treatment
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* Radiation: whole brain radiation(WBI)
* Drug: Icotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who was confirmed stage IV NSCLC with EGFR activating mutation and brain metastases by pathologic histology or cytology. Patient who brain metastases was shown in MRI or CT scan. Brain metastases lesions should be more than 3.The diameter among these lesions should be more than 1 centimeter. Males or females aged ≥18 years, < 75 years. Eastern Cooperative Oncology Group(ECOG) performance status 0-1. Life expectancy ≥12 weeks. The therapy of surgery,chemotherapy,radiotherapy that the patients were ever received should be more than 2 weeks ago.The patient had recovered from the treatment. Males and females should be contraceptive during the period of the trial until 8 weeks after the last administration of icotinib. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications. Written informed consent provided. Exclusion Criteria: Patient was received irradiation of brain. Patient with meningeal metastases were confirmed by MRI or cytology test of cerebrospinal fluid. Patient is received the treatment of Phenytoin, carbamazepine, rifampicin, phenobarbital, or St. John's Wort. Patient was received EGFR Tyrosine Kinase Inhibitor or EGFR monoclonal antibody. Interstitial pneumonia.Pericardial effusion, pleural effusion is uncontrolled . Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease). Any significant ophthalmologic abnormality ,especially severe dry eye syndrome ,keratoconjunctivitis sicca,Sjogren syndrome,severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease. Female subjects should not be pregnant or breast-feeding. Adequate hematological function: Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥100 x 109/L. Adequate renal function: Serum creatinine ≤ 1.5 x ULN, or ≥ 50 ml/min. Adequate liver function :Total bilirubin £ 1.5 x upper limit of normal (ULN) and Alanine Aminotransferase (ALT )and Aspartate Aminotransferase (AST )< 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases. The symptoms of increased intracranial pressure are uncontrolled after dehydration and cortisone treatment. Patient need increase irradiation dose after routine irradiation(30GY/10f/2w) Patient should treat extra cranial lesions first. Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

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<br>icotinib administered orally at a dose of 125 mg 3 times daily | Drug: Icotinib<br>* administered orally at a dose of 125 mg 3 times daily<br>|
| Active Comparator: Whole brain irradiation<br>Whole brain irradiation 30Gy/3Gy/10 fractions plus concurrent or sequential chemotherapy for 4-6 cycles | Radiation: whole brain radiation(WBI)<br>* WBI (30Gy/3Gy/10 fractions) plus concurrent or sequential chemotherapy for 4-6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iPFS | intracranial progression-free survival | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival (PFS) | progress-free survival | up to 16 months | 
| time of controlling brain metastasis symptom | time of controlling brain metastasis symptom | 18months | 
| Response rate of brain metastasis | Response rate of brain metastasis | 12months | 
| Cognitive function | Cognitive function | 18months | 
| overall survival(OS) | overall survival(OS) | 24months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR mutant