Icotinib Combined With WBRT For NSCLC Patients With Brain Metastases and EGFR Mutation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of Icotinib at different dose levels in combination with whole brain radiotherapy for NSCLC patients with brain metastases and EGFR mutation.

Detailed Description
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The long-term control of brain metastases becomes a clinical challenge. Whole brain radiotherapy, the standard treatment for patients with multiple brain metastases, can only bring a modest survival improvement around 3-6 months. EGFR-TKIs like icotinib with its proven activity in non-small cell lung cancer may provide clinical benefits in such patients.

Official Title
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A Single Center, Open Label, Dose-Finding Study to Determine the Safety of Icotinib in Combination With Whole Brain Radiation Therapy For NSCLC Patients With Brain Metastases and EGFR Mutation.

Conditions
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Non-small Cell Lung Cancer, Brain Metastases

Intervention / Treatment
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* Drug: icotinib
* Radiation: Whole brain radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmation of non-small cell lung cancer (NSCLC). Diagnosis of brain metastases on a Gadolinium-enhanced MRI. More than 3 sites of intracranial metastases, or the longest diameter of the intracranial lesion is more than 3cm. Positive EGFR mutation. Exclusion Criteria: Previous usage of EGFR-TKI or antibody to EGFR: gefitinib, erlotinib, herceptin, erbitux. CSF or MRI findings consistent with metastases of spinal cord, meninges or meningeal.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Icotinib+WBRT<br>Standard whole brain radiotherapy plus icotinib, which is designed to administered at 5 dose according to 3+3 until disease progression or intolerable toxicity. | Drug: icotinib<br>* Level 1: Standard whole brain radiation therapy plus icotinib 125 mg Tid (375 mg per day) from day1 until disease progression or intolerable toxicity. Level 2: Standard whole brain radiation therapy plus icotinib 250 mg Tid (750 mg per day) from day1 until disease progression or intolerable toxicity. Level 3: Standard whole brain radiation therapy plus icotinib 375 mg Tid (1125 mg per day) from day1 until disease progression or intolerable toxicity. Level 4:Standard whole brain radiation therapy plus icotinib 500 mg Tid (1500 mg per day) from day1 until disease progression or intolerable toxicity.<br>* Other names: BPI-2009, Conmana;Radiation: Whole brain radiotherapy<br>* Whole Brain Radiation Therapy (WBRT) for total dose of 37.5Gy in 15 daily fractions beginning after Day 7.<br>* Other names: WBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | All cause adverse events (AEs) and serious adverse events (SAEs) | 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological progression-free survival | All cause neurological progress or mortality | 3-6 month | 
| Progression-free survival | All cause progress or mortality | 3-6 months | 
| Overall survival | All cause mortality | 6-12 months | 
| Response rate |  | 3-6 month | 
| Quality of life measured by FACT-L/LCS 4.0 |  | 1 year | 
| Neurocognitive effects | Evaluated according to Mini-Mental Status Examination | 3-6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, EGFR-TKI, NSCLC, Icotinib, WBRT