Bevacizumab Combined With Fractionated Stereotactic Radiotherapy for 1 to 10 Brain Metastases From NSCLC

Study Overview
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Brief Summary
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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-small cell lung cancer by assessing the treatment response, perilesional edema, neurological symptoms and quality of life.

Detailed Description
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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-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. The primary endpoint was intra-cranial progression-free survival (IPFS). Secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life (QOL) scores, and toxicities.

Official Title
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A Prospective, Phase II Study of Bevacizumab Combined With Fractionated Stereotactic Radiotherapy in Patients With 1 to 10 Brain Metastases From Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Combination Product: FSRT combined with Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged ≥18 years old; histologically confirmed NSCLC; 1-10 BMs on contrast-enhanced MRI; stable extracranial disease status at the time of enrollment; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 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: Intracranial metastases needed surgical decompression Patients with contraindications for MRI Previous radiotherapy or excision for intracranial metastases 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FSRT & Bevacizumab<br>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) | Combination Product: FSRT combined with Bevacizumab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial progression-free survival | IPFS was calculated from the completion of radiotherapy until the first occurrence of either intracranial progression or death. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) |  | 1 year | 
| progression-free survival (PFS) |  | 1 year | 
| Rate of participants with perilesional edema of brain metastases evaluated by T2-weighted MRI |  | 1 year | 
| Quality of life evaluated by EORTC quality of life questionnaire | Quality of life evaluated by EORTC quality of life questionnaire(QLQ-C30 and QLQ-BN20) | 6 months | 
| Rate of patients with treatment-related adverse events evaluated by CTCAE v5.0 |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, Bevacizumab, Fractionated stereotactic radiation therapy, Brain metastases