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

Primary Purpose

Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
FSRT combined with Bevacizumab
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring non-small cell lung cancer, Bevacizumab, Fractionated stereotactic radiation therapy, Brain metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sun Yat-sen University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FSRT & Bevacizumab

Arm Description

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

overall survival (OS)
progression-free survival (PFS)
Rate of participants with perilesional edema of brain metastases evaluated by T2-weighted MRI
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)
Rate of patients with treatment-related adverse events evaluated by CTCAE v5.0

Full Information

First Posted
February 22, 2020
Last Updated
August 25, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT04345146
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
March 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
non-small cell lung cancer, Bevacizumab, Fractionated stereotactic radiation therapy, Brain metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FSRT & Bevacizumab
Arm Type
Experimental
Arm Description
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)
Intervention Type
Combination Product
Intervention Name(s)
FSRT combined with Bevacizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Intracranial progression-free survival
Description
IPFS was calculated from the completion of radiotherapy until the first occurrence of either intracranial progression or death.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
overall survival (OS)
Time Frame
1 year
Title
progression-free survival (PFS)
Time Frame
1 year
Title
Rate of participants with perilesional edema of brain metastases evaluated by T2-weighted MRI
Time Frame
1 year
Title
Quality of life evaluated by EORTC quality of life questionnaire
Description
Quality of life evaluated by EORTC quality of life questionnaire(QLQ-C30 and QLQ-BN20)
Time Frame
6 months
Title
Rate of patients with treatment-related adverse events evaluated by CTCAE v5.0
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hui Liu, Ph.D
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University
City
Guangzhou
ZIP/Postal Code
510000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
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Bevacizumab Combined With Fractionated Stereotactic Radiotherapy for 1 to 10 Brain Metastases From NSCLC

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