Icotinib Combined With Whole Brain Radiotherapy in Treating Multiple Brain Metastases From Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to explore the efficacy and toxicity of icotinib combined with WBRT in treating patients with multiple brain metastases from NSCLC.

Detailed Description
-----------------
Brain metastases occur in 25-40% of patients with non-small cell lung cancer (NSCLC). It is one of the primary reasons resulting in treatment failure and the death. Whole-brain radiation therapy (WBRT) is the standard approach to the treatment of multiple brain metastases from NSCLC. Regardless of the treatment of brain metastases by WBRT combined with systemic chemotherapy,outcomes of NSCLC with brain metastases are still very poor. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can pass through the blood-brain barrier and show promising antitumor activity against brain metastases from NSCLC. Icotinib shows nearly the same effect as gefitinib in advanced NSCLC patients failed with chemotherapy.

Official Title
-----------------
Phase II Study of Icotinib Combined With Whole Brain Radiotherapy in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Drug: Icotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Cytologic or histological diagnosis of non-small cell lung cancer Patients with disease progression after systemic chemotherapy with two-drug combination regimens that includes a platinum agent or patients with EGFR mutation status who have not been treated Patients are diagnosed with multiple brain metastases for the first time in 4 weeks Diagnosis of brain metastases is made based on Magnetic resonance imaging (MRI). Doctors consider the patient will benefit from WBRT No prior brain radiotherapy ECOG performance status 0-2 age:18-75 years Neutrophil count ≥1.5×10 to the 9th power/L and platelets≥100×10 to the 9th power/L. hemoglobin ≥90 g/L Hepatic: total bilirubin less than or equal to 1.5 times upper limit of normal (ULN) Alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN (or less than or equal to 5 times ULN in case of known liver involvement) Renal: Serum Creatinine less than or equal to 1.5 times upper limit of normal (ULN) Patients with measurable brain metastases according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Patients must sign an informed consent indicating that they are aware of the investigational nature of the study Exclusion Criteria: Prior brain radiation therapy Solitary brain metastasis according to Magnetic resonance imaging (MRI) Mort than 3 extracranial organs have metastatic lesions Prior invasive malignancy (skin basal cell cancer, carcinoma in situ of cervix are permissible). pregnant or breast feeding women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Icotinib plus Whole Brain Radiotherapy<br>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have shown efficacy in advanced non-small cell lung cancer (NSCLC) patients with brain metastases (BM). Icotinib is a new first generation EGFR-TKI. We conducted a phase II study to evaluate the efficacy and safety of icotinib in combination with whole brain radiotherapy （WBRT） in Chinese NSCLC patients with BM and investigated the cerebrospinal fluid (CSF)/ plasma concentrations of icotinib. | Drug: Icotinib<br>* Patients will receive whole brain radiotherapy therapy 30Gy over 10 fractions and icotinib will be administered at the beginning of whole brain radiotherapy in doses of 125 mg thrice per day until disease progression or undue toxicity.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| partial response rate of intracranial lesions | Partial response rate of intracranial lesions will be measured. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival will be evaluated | 4 years | 
| overall survival | Overall survival will be evaluated | 4 years | 
| partial response rate of extracranial lesions | Partial response rate of extracranial lesions will be evaluated | 2 years | 
| Health-related quality of life | Health-related quality of life will be measured | 2 years | 
| safety and tolerability | Safety and tolerability of Icotinib and whole brain radiotherapy will be monitored by evaluation of frequency,severity,and duration of treatment-emergent adverse events in all subjects | 4 year | 
| the relationship between Progression-Free Survival and EGFR mutation status | The relationship between Progression-Free Survival and EGFR mutation status will be evaluated. | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tumors metastatic to brain, non-small cell lung cancer, Icotinib