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

Phase 2

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Combination Product: FSRT combined with Bevacizumab

• Registration Number: NCT04345146
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-01-01
• Study First Submitted: 2020-02-22
• Study First Submitted QC: 2020-04-10
• Study First Posted: 2020-04-14
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-25
• Last Update Posted: 2023-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FSRT & Bevacizumab	FSRT combined with 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)

Primary Outcome Measures

Name	Time	Method
Intracranial progression-free survival	1 year	IPFS was calculated from the completion of radiotherapy until the first occurrence of either intracranial progression or death.

Secondary Outcome Measures

Name	Time	Method
overall survival (OS)	1 year
progression-free survival (PFS)	1 year
Rate of patients with treatment-related adverse events evaluated by CTCAE v5.0	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	6 months	Quality of life evaluated by EORTC quality of life questionnaire(QLQ-C30 and QLQ-BN20)

Trial Locations

Locations (1)

Sun Yat-sen University; 🇨🇳 Guangzhou, China