Hypofractionated Brain Radiation In EGFR Mutated Adenocarcinoma Cranial Disease (Hybrid)
- Conditions
- Stage IV EGFR Mutated NSCL With Brain Metastases
- Interventions
- Radiation: HFSRSRadiation: WBRT
- Registration Number
- NCT02882984
- Lead Sponsor
- Sichuan Provincial People's Hospital
- Brief Summary
A multi-center phase III randomized controlled study to evaluate the efficacy of Hypofractionated SRS (HFSRS) along with EGFR-TKI in patients with brain metastasis from non-small cell lung cancer (NSCLC). Assuming that HFSRS 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), evaluation of cognitive function, quality of life (QoL) and adverse events.
- Detailed Description
WBRT remains to be standard of care for NSCL patients. Long term survival from WBRT may have noticeable cognitive dysfunction. The EGFR TKI has reasonable control for intracranial disease, but the duration of EGFR TKI control disease is variable due to tendency of drug resistance. To maintain intracranial disease control and improve cognitive function, the investigators propose using hypofractionated SRS in multiple brain metastases or large brain lesions alone with TKI.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 325
- 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 4 cm.
- Positive EGFR mutation.
- Life expectancy ≥3months.
- Have one or more measurable encephalic lesions according to RECIST.
- 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.
- Female subjects should not be pregnant.
- All human subjects should able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
- Written informed consent provided.
- 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.
- Allergic to Icotinib.
- Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
- Pregnancy or breast-feeding women.
- Participate in the other anti-tumor clinical trials in 4 weeks.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HFSRS with EGFR TKI HFSRS Drug: EGFR-TKI Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib Radiation: whole brain radiotherapy 25 to 40 Gy/5F Other Name: HFSRS WBRT along with TKI WBRT Drug: EGFR-TKI Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib Radiation: whole brain radiotherapy 3750Gy/15F Other Name: WBRT
- Primary Outcome Measures
Name Time Method iPFS 18 months intracranial progression-free survival
- Secondary Outcome Measures
Name Time Method cognitive function 18 month Neurocognitive effects evaluated according to Mini-Mental Status Examination Evaluated according to Mini-Mental Status Examination
Overall survival (OS) 18 months Overall survival
Trial Locations
- Locations (1)
Sichuan PPH, Cancer Center
🇨🇳Chengdu, Sichuan, China