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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT02714010

Collaborator

(none)

601

Enrollment

Location

Arms

Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: EGFR-TKI Radiation: whole brain radiotherapy	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

601 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

intracranial PFS (iPFS) [up to 41 months]
Compare intracranial PFS (iPFS) of two arms

Secondary Outcome Measures

overall survival (OS) [up to 77 months]
objective response rate (ORR) [up to 41 months]

Other Outcome Measures

cognitive impairment [up to 77 months]
questionnaire
quality of life (QoL) [up to 77 months]
questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.