Clinical trial NCT04345146: Bevacizumab Combined With Fractionated Stereotactic Radiotherapy for 1 to 10 Brain Metastases From NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: non-small cell lung cancer
Bevacizumab
Fractionated stereotactic radiation therapy
Brain metastases
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intracranial progression-free survival
timeFrame: 1 year
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 1 year
measure: progression-free survival (PFS)
timeFrame: 1 year
measure: Rate of participants with perilesional edema of brain metastases evaluated by T2-weighted MRI
timeFrame: 1 year
measure: Quality of life evaluated by EORTC quality of life questionnaire
timeFrame: 6 months
measure: Rate of patients with treatment-related adverse events evaluated by CTCAE v5.0
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University
Study officials:
affiliation: Sun Yat-sen University
name: Hui Liu, Ph.D
role: PRINCIPAL_INVESTIGATOR
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