Clinical trial NCT02882984: Hypofractionated Brain Radiation In EGFR Mutated Adenocarcinoma Cranial Disease (Hybrid)
Official title: Comparing Whole Brain Radiation With Hypofractionated Stereotactic RadioSurgery (HFSRS) in Patients With NSCL Brain Metastases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Stage IV EGFR Mutated NSCL With Brain Metastases
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2016-08-30
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: iPFS
timeFrame: 18 months
Secondary outcomes:
measure: cognitive function
timeFrame: 18 month
measure: Overall survival (OS)
timeFrame: 18 months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan PPH, Cancer Center
state: Sichuan
Study officials:
affiliation: Sichuan Provincial People Hospital, Sichuan Academy of Medical Sciences
name: Ming Zeng, MD PhD
role: STUDY_CHAIR
References: