EGFR-TKI Concurrent With/Without WBRT in Brain Metastasis From NSCLC

Study Overview
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Brief Summary
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This is a multi-center phase III randomized controlled study, designing to access whether the efficacy of EGFR-TKI alone on patients with brain metastasis from non-small cell lung cancer (NSCLC) harboring EGFR mutant type is not inferior to EGFR-TKI concurrent with whole brain radiotherapy (WBRT), the primary end point is intracranial PFS (iPFS), while secondary outcomes included overall survival (OS), objective response rate (ORR), evaluation of cognitive function, quality of life (QoL) and adverse events.

Official Title
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Whole Brain Radiotherapy Concurrent With EGFR-TKI Versus EGFR-TKI Alone in the Treatment of Non-small Cell Lung Cancer Patients With Brain Metastasis

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: EGFR-TKI
* Radiation: whole brain radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who was confirmed non-small cell lung cancer (NSCLC) by histology or cytology, harboring EGFR mutant type (19 and/or 21 exon mutation). Patients who was confirmed with asymptomatic, treatment naive brain metastasis (didn't receive any treatment after diagnosed with brain metastasis) by MRI, couldn't receive operation or stereotactic radiosurgery（SRS）. Appraisable disease, that is there must be at least one lesion with the longest diameter>10mm in brain (by brain MRI). Adult patients (18 to 75 years old). Eastern Cooperative Oncology Group（ECOG） performance status 0 to 2. Life expectancy of at least 12 weeks. Haemoglobin > 10g/dl, absolute neutrophil count (ANC) > 1.5 x 10^9/L, platelets > 100 x 10^9/L; total bilirubin < 1.5x upper limit of normal (ULN). Alanine aminotransferase（ALT） and aspartate aminotransferase（AST）< 1.5x ULN in the absence of liver metastases, or < 5x ULN in case of liver metastases. Creatinine clearance > 60ml/min (calculated according to Cockcroft-gault formula). Patients should be contraceptive during the period of the trial. Exclusion Criteria: Patients who had received brain radiotherapy or EGFR-TKI before. Patients who can't receive WBRT. Uncontrolled intracranial hypertension after steroid or dehydration therapy. Patients who take phenytoin, Carbamazepine, Rifampicin, Barbital, or St John's Wort which will interfere with the metabolism of TKI. Patients with interstitial lung disease, significant ocular disease, or serious uncontrolled systematic disease. Patients who can't take oral tablets, with active peptic ulcer diseases. Pregnancy or breast-feeding women.

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: Arm 1<br>Patients take EGFR-TKI alone till tumor progression | Drug: EGFR-TKI<br>* Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid<br>* Other names: Gefitinib/Tarceva/Icotinib;|
| Active Comparator: Arm 2<br>Patients take EGFR-TKI concurrent with whole brain radiotherapy (WBRT) till tumor progression, WBRT started within the first week of taking TKI | Drug: EGFR-TKI<br>* Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid<br>* Other names: Gefitinib/Tarceva/Icotinib;Radiation: whole brain radiotherapy<br>* 30Gy/10F<br>* Other names: WBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial PFS (iPFS) | Compare intracranial PFS (iPFS) of two arms | up to 41 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) |  | up to 77 months | 
| objective response rate (ORR) |  | up to 41 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR-TKI, whole brain radiotherapy, brain metastasis, non-small cell lung cancer