Icotinib or Whole Brain Irradiation in EGFR-mutant Lung Cancer (BRAIN)

Phase III Study of Icotinib Treat the Patient With Brain Metastasis EGFR-mutant Non Small Cell Lung Cancer Comparing With Whole Brain Radiotherapy

EGFR-TKI is good for the patients with EGFR-mutant non-small cell lung cancer.We design this clinical trail to confirm if the efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI )(ICOTINIB) is better than whole brain irradiation for the patient with EGFR-mutant non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer; Brain Metastasis
• Intervention / Treatment: Drug: Icotinib; Radiation: whole brain radiation(WBI)

Detailed Description

no available

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patient who was confirmed stage IV NSCLC with EGFR activating mutation and brain metastases by pathologic histology or cytology.

Patient who brain metastases was shown in MRI or CT scan. Brain metastases lesions should be more than 3.The diameter among these lesions should be more than 1 centimeter.

Males or females aged ≥18 years, < 75 years. Eastern Cooperative Oncology Group(ECOG) performance status 0-1. Life expectancy ≥12 weeks. The therapy of surgery,chemotherapy,radiotherapy that the patients were ever received should be more than 2 weeks ago.The patient had recovered from the treatment.

Males and females 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.

Written informed consent provided.

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.

Female subjects should not be pregnant or breast-feeding. Adequate hematological function: Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥100 x 109/L.

Adequate renal function: Serum creatinine ≤ 1.5 x ULN, or ≥ 50 ml/min. Adequate liver function :Total bilirubin £ 1.5 x upper limit of normal (ULN) and Alanine Aminotransferase (ALT )and Aspartate Aminotransferase (AST )< 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases.

The symptoms of increased intracranial pressure are uncontrolled after dehydration and cortisone treatment.

Patient need increase irradiation dose after routine irradiation(30GY/10f/2w) Patient should treat extra cranial lesions first. Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: icotinib; icotinib administered orally at a dose of 125 mg 3 times daily	Drug: Icotinib; administered orally at a dose of 125 mg 3 times daily
Active Comparator: Whole brain irradiation; Whole brain irradiation 30Gy/3Gy/10 fractions plus concurrent or sequential chemotherapy for 4-6 cycles	Radiation: whole brain radiation(WBI); WBI (30Gy/3Gy/10 fractions) plus concurrent or sequential chemotherapy for 4-6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS	intracranial progression-free survival	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progress-free survival (PFS)	progress-free survival	up to 16 months
time of controlling brain metastasis symptom	time of controlling brain metastasis symptom	18months
Response rate of brain metastasis	Response rate of brain metastasis	12months
Cognitive function	Cognitive function	18months
overall survival(OS)	overall survival(OS)	24months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	adverse events(according to CTC4.0)	24months

Collaborators and Investigators

• Sponsor: Guangdong Association of Clinical Trials
• Collaborators: Guangdong Provincial People's Hospital
• Investigators: Study Director: Jinji Yang, MD, Guangdong Provincial People's Hospital

Publications and helpful links

General Publications

• Yang JJ, Zhou C, Huang Y, Feng J, Lu S, Song Y, Huang C, Wu G, Zhang L, Cheng Y, Hu C, Chen G, Zhang L, Liu X, Yan HH, Tan FL, Zhong W, Wu YL. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial. Lancet Respir Med. 2017 Sep;5(9):707-716. doi: 10.1016/S2213-2600(17)30262-X. Epub 2017 Jul 19.

Study record dates

Study Major Dates

• Study Start: October 14, 2012
• Primary Completion (Actual): June 30, 2015
• Study Completion (Actual): September 14, 2016

Study Registration Dates

• First Submitted: October 14, 2012
• First Submitted That Met QC Criteria: November 7, 2012
• First Posted (Estimate): November 12, 2012

Study Record Updates

• Last Update Posted (Actual): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: EGFR mutant
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: CTONG1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided