Assess the Efficacy of Whole Brain Radiation Therapy in Lung Cancer Patients With Brain Metastasis

Study Overview
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Brief Summary
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Multicentre randomised (1:1) trial assessing the efficacy of whole brain radiotherapy in addition to Gefitinib for the management of brain metastasis in lung cancer patients with a mutated EGFR.

Detailed Description
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Lung cancer patients with newly diagnosed CNS metastasis with- at least one brain lesion measuring > 1 cm in longest dimension - not eligible for surgery or stereotactic radio-surgeryOpen-label, multicentre, national, randomised (1:1) phase II trialArm A: WBRT and Concurrent Gefitinib followed by Gefitinib Maintenance Arm B: Gefitinib

Official Title
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Randomized to Assess the Efficacy of Whole Brain Radiation Therapy (WBRT) With Concomitant Gefitinib Followed by Maintenance Gefitinib, and Gefitinib Alone, in Lung Cancer Patients With Brain Metastasis

Conditions
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EGFR-mutated Lung Adenocarcinoma, Brain Metastasis

Intervention / Treatment
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* Other: whole brain radiotherapy
* Drug: Gefitinib (IRESSA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have signed a written informed consent form prior to any study specific screening procedures 18 years or older KPS ≥ 50% Histologically confirmed adenocarcinoma of the lung Activating mutation of EGFR Newly diagnosed CNS metastasis or in progression with at least one measurable lesion in the brain (defined as any lesion > 1 cm on T1-weighted contrast enhanced MRI) Patients could enter the study regardless of previous treatment (included chemotherapy) for metastatic extracranial disease, except TKI. No steroids or stable or decreasing dose of steroids for at least 5 days before the MRI evaluation. Adequate hematologic, liver and renal functions: neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; Hb ≥ 9 g/Dl; Total bilirubin < 1.5 x ULN; AST or ALT < 2.5 x ULN (< 5 x ULN in patients with liver metastases); Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min Exclusion Criteria: Prior treatment of brain metastases with WBRT or TKI Patient eligible for radiosurgery or surgical resection Contre indication at the radiotherapy Leptomeningeal disease Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix) within the the 5 years before study entry Prior treatment with Gefitinib or other TKI Pregnant or breast feeding women Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception

Ages Eligible for Study
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Minimum Age: 18 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 A : Gefitinib + WBRT<br>Arm A : WBRT and Concurrent Gefitinib followed by Gefitinib Maintenance | Other: whole brain radiotherapy<br>* External beam RT using a total dose of 30 Gy with ten daily fractions of 3.0 Gy given 5 days per week over 2 weeks + Gefitinib 250 mg/day<br>|
| Experimental: Arm B : Gefitinib<br>Arm B : Gefitinib alone | Drug: Gefitinib (IRESSA)<br>* 250 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the objective response rate of brain metastases in each arm |  | at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with neurological Adverse Events |  | at 6 weeks, 3 months, 4.5 months and 6 months | 
| Progression-free survival (PFS) |  | at 6 months | 
| Overall survival |  | at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized, Brain Radiation Therapy, Lung Cancer, Brain Metastasis, Gefitinib