Gefitinib With or Without Chemotherapy in Brain Metastases From Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a multi-center phase III randomized controlled study to assess the efficacy of Gefitinib alone and Gefitinib combination with Pemetrexed/platinum on patients with brain metastasis from non-small cell lung cancer(NSCLC) harboring EGFR mutation type by intracranial PFS(iPFS),also PFS ,DCR and OS.The side effect is evaluated as well.

Official Title
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Multicenter Phase III Study of Gefitinib Mono-therapy or Gefitinib Combined With Chemotherapy in Patients With Brain Metastases From Non-small Cell Lung Cancer Harboring EGFR Mutation

Conditions
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EGFR Mutation, Non-small Cell Lung Cancer, Brain Metastases

Intervention / Treatment
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* Drug: Gefitinib and Pemetrexed/platinum
* Drug: Gefitinib mono-therapy


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 Patients who had never received therapy (including chemotherapy,WBRT,EGFR-TKI and EGFR monoclonal antibody) after diagnosed brain metastases Patients had at least three metastatic lesions in brain, or patients with 1-2 intracranial lesions who were not suitable for brain radiotherapy, or patients with 1-2 intracranial lesions who refused brain radiotherapy, at least one intracranial lesion with the longest diameter of >5 mm Adult patients (≥ 18 years and ≤75 years). ECOG Performance Status 0 or 1 Life expectancy of at least 12 weeks.,Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count (ANC) ³1.5 x 109/L, platelets ³ 100 x 109/L. Total bilirubin £ 1.5 x upper limit of normal (ULN). ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases. Creatinine clearance ³ 60ml/min (calculated according to Cockcroft-gault formula). Patients 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. 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. The symptoms of increased intracranial pressure are uncontrolled after dehydration and cortisone treatment

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: Gefitinib and Pemetrexed/platinum<br>Gefitinib 250mg is Taken Orally on day 1-28,combined Pemetrexed (D1)+cisplatin (D1-3) chemotherapy or Pemetrexed (D1)+nedaplatin (D1) chemotherapy, every 28 days | Drug: Gefitinib and Pemetrexed/platinum<br>* Gefitinib 250mg is Taken Orally on day 1-28,combined Pemetrexed (D1)+cisplatin (D1-3) or Pemetrexed (D1) + nedaplatin (D1) chemotherapy, every 28 days<br>|
| Active Comparator: Gefitinib mono-therapy<br>Gefitinib 250mg is Taken Orally everyday | Drug: Gefitinib mono-therapy<br>* Gefitinib 250mg is Taken Orally everyday<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iPFS(intracranial progression free survival | defined as time from randomization to intracranial progressive disease or death. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | proportion of patients with complete or partial response of overall lesions | 2 years | 
| intracranial objective response rate (iORR) | proportion of patients with complete or partial response of intracranial lesions | 2 years | 
| PFS(Progression Free Survival) | time from randomization to overall disease progression or death | 2 years | 
| OS(Overall Survival) | time from randomization to death from any cause | 3 years | 
| adverse events | adverse events were evaluated according to NCI-CTCAE 4.0. | 3 years |