Clinical Trial Finder

Inclusion Criteria:

• - Histologically confirmed non-squamous non-small cell lung cancer.

• - 1-10 metastases on contrast-enhanced MRI.

• - No anti-angiogenic therapy within previous 90 days.

• - Radiotherapy for extracranial lesions is permitted.

• - Tyrosine kinase inhibitors (TKI) are permitted in patients with progression of intracranial metastases during previous TKI therapy.

• - Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

• - Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• - Normal function of organs and bone marrow within 14 days: Total bilirubin 1.5 times or less the upper limits of normal (ULN); AST and ALT 1.5 times or less the ULN; absolute neutrophil count≥ 500 cells/mm3; creatinine clearance rate(CCR) ≥45 mL/min; Platelet count≥50,000 cells/mm3; international normalized ratio(INR) ≤1.5，Prothrombin Time (PT)≤ 1.5 × ULN.

• - Informed-consent.

Exclusion Criteria:

• - Squamous cell carcinoma or small cell carcinoma of lung.

• - Intracranial metastases needed surgical decompression.

• - Patients with contraindications for MRI.

• - Previous radiotherapy or excision for intracranial metastases.

• - Chemotherapy, immunotherapy or biotherapy within 7 days before or after fractionated stereotactic radiotherapy.

• - The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava) - A cavity over 2cm in diameter of primary tumor or metastasis.

• - Bleeding tendency or coagulation disorder.

• - Hemoptysis (1/2 teaspoon blood/day) happened within 1 month.

• - The use of full-dose anticoagulation within the past 1 month.

• - Severe vascular disease occurred within 6 months.

• - Gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months.

• - Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months.

• - Uncontrolled hypertension (systolic > 150mmHg and/or diastolic > 100mmHg) - Major surgery within 28 days or minor surgery or needle biopsy within 48 hours.

• - Urine protein 3-4+, or 24h urine protein quantitative >1g.

• - Severe uncontrolled disease.

• - Uncontrollable seizure or psychotic patients without self-control ability.

• - Women in pregnancy, lactation period.

- Other not suitable conditions determined by the investigators

This Phase II randomized study is to determine the efficacy and safety of Bevacizumab combined with fractionated stereotactic radiation therapy(FSRT) in patients with 1 to 10 brain metastases in non-squamous non-small cell lung cancer by assessing the treatment response, neurological symptoms and quality of life. Patients will receive Bevacizumab(7.5mg/kg, q3w, i.v.) before and after FSRT(40Gy in 10 fractions or 30Gy in 5 fractions) to the brain metastases with Bevacizumab (7.5mg/kg, q3w, IV). The primary end point is the objective response rate. The secondary end points are 1-y iPFS, 1-y PFS, 1-y OS, perilesional edema of brain metastases, neurological symptoms, quality of life and safety of the treatment.

Arms

Experimental: FSRT & Bevacizumab

Patients will receive Bevacizumab before and after FSRT: daily FSRT(40Gy in 10 fractions or 30Gy in 5 fractions) to the brain metastases with Bevacizumab(7.5mg/kg, q3w, IV)

Interventions

Combination Product: - FSRT combined with Bevacizumab

Bevacizumab: Patients will receive Bevacizumab (7.5mg/kg, q3w, IV) before and after FSRT. Fractionated stereotactic radiotherapy(FSRT): 40 Gy/10 fractions or 30 Gy/5 fractions for GTV will be delivered to brain metastases.