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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: EGFR-TKI; Radiation: whole brain radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 601
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University of Cancer Center
      • Contact: li-kun chen, doctor; Phone Number: 13798019964

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:

• 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.

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: Arm 1; Patients take EGFR-TKI alone till tumor progression	Drug: EGFR-TKI; Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid; Other Names: Gefitinib/Tarceva/Icotinib
Active Comparator: Arm 2; 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; Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid; Other Names: Gefitinib/Tarceva/Icotinib; Radiation: whole brain radiotherapy; 30Gy/10F; Other Names: WBRT

What is the study measuring?

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	Time Frame
overall survival (OS)	up to 77 months
objective response rate (ORR)	up to 41 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive impairment	questionnaire	up to 77 months
quality of life (QoL)	questionnaire	up to 77 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: li-kun Chen, associate chief physician

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: November 29, 2015
• First Submitted That Met QC Criteria: March 15, 2016
• First Posted (Estimate): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; whole brain radiotherapy; brain metastasis; EGFR-TKI
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: GASTO1014