FSRT Combines With Bevacizumab for Multiple Brain Metastases in Lung Adenocarcinoma

NCT07058428 | Recruiting Phase 3

• 1 other identifier: GASTO-10137
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 1

Brief Summary

For non-small cell lung cancer brain metastases, stereotactic radiotherapy is gradually replacing whole brain radiotherapy as the standard treatment. When patients have multiple brain metastases or larger tumors (diameter\>2cm), single session stereotactic radiotherapy (SRS) may cause significant neurological damage, so fractionated stereotactic radiotherapy (FSRT) is often used. The recent objective remission rate of FSRT is about 50%, and the 1-year intracranial control rate is about 45%, but intracranial progression remains the main factor affecting long-term survival of patients. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor, which can improve the efficacy of cranial radiotherapy by normalizing neovascularization and improving the hypoxic state of tumor cells. In addition, bevacizumab can improve the abnormal permeability of neovascularization, reduce exudation and extracellular brain edema, thereby further alleviating the toxic side effects associated with brain radiotherapy. Based on this, this prospective, controlled phase III study will explore the efficacy and safety of the combined use of fractionated stereotactic radiotherapy and bevacizumab in multiple brain metastases of lung adenocarcinoma.

Conditions

Multiple Brain Metastases in Lung Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Intracranial progression free survival

  the time interval from the end of radiotherapy to the first occurrence of intracranial progression or death or the last follow-up;

  2 years

Secondary Outcomes (5)

• Progress free survival

  2 years

• Overall survival

  2 years

• The quality of life (QOL)

  2 years

• Treatment related side effects

  2 years

• Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure

  6 months

Study Arms (3)

The FSRT+beva group

EXPERIMENTAL

The FSRT+beva group receives FSRT radiotherapy+bevacizumab treatment; FSRT targets visible intracranial lesions with a total dose of 30Gy, administered once a day for a total of 5 times, with a single dose of 6Gy. Bevacizumab starts on day 1 (one week before FSRT treatment), q3w， A total of 4 treatment courses, intravenous injection, with a dose of 7.5mg/kg.

Drug: Bevacizumab; Radiation: FSRT

The FSRT group

ACTIVE COMPARATOR

The FSRT group receives simple FSRT radiotherapy; FSRT is targeted at visible intracranial lesions, with a total dose of 30Gy, administered once a day for a total of 5 days, with a fraction dose of 6Gy.

Radiation: FSRT

The WBRT group

ACTIVE COMPARATOR

The WBRT group receive whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) to visible intracranial lesions. The prescribed doses are: 40 Gy total to gross lesions and 25 Gy total to the whole brain, delivered in 10 daily fractions.

Radiation: Whole brain radiotherapy

Interventions

Bevacizumab DRUG

Bevacizumab starts on day 1 (one week before FSRT treatment), q3w，a total of 4 treatment courses, intravenous injection, with a dose of 7.5mg/kg.

The FSRT+beva group

FSRT RADIATION

The FSRT group received simple FSRT radiotherapy; FSRT is targeted at visible intracranial lesions, with a total dose of 30Gy, administered once a day for a total of 5 days, with a fraction dose of 6Gy.

The FSRT group; The FSRT+beva group

Whole brain radiotherapy RADIATION

The WBRT group received whole brain radiotherapy and locally increased dose radiotherapy for visible intracranial lesions, with a total dose of 40Gy for local lesions and 25Gy for the whole brain, once a day for a total of 10 days.

The WBRT group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old;
• Cellular or histopathological confirmation of lung adenocarcinoma;
• Prior to enrollment, brain enhanced magnetic resonance imaging shows (1) 1-2 brain metastases, with at least one measuring ≥3 cm in diameter; or (2) 3-10 brain metastases, with at least one measuring ≥2 cm in diameter; or (3) 11-20 brain metastases; and deemed unsuitable for single-session SRS by radiation oncologists;
• At the time of enrollment, the extracranial disease status is stable;
• Eastern Cooperative Oncology Group (ECOG) physical fitness status score 0-2 points
• Normal liver, kidney, and bone marrow function within 14 days prior to enrollment: peripheral blood white blood cell count ≥ 4 × 10\^9/L; neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin ≥ 100g/L, serum creatinine\<1.5 times the upper limit of normal values; Bilirubin\<1.5 times the upper limit of normal value; Transaminase\<2 times the upper limit of normal value;
• The patient and their family agree and sign an informed consent form.

You may not qualify if:

• There are contraindications for bevacizumab, such as a history of cardiac and/or thromboembolic events, or uncontrolled hypertension;
• Meningeal metastasis or extensive intracranial metastasis are not suitable for FSRT;
• Bleeding tendency or coagulation dysfunction;
• Patients with hemoptysis (≥ 1/2 teaspoon of fresh blood per day) within the past month;
• Use full dose anticoagulant therapy within the past month;
• Has experienced severe vascular disease in the past 6 months;
• Have experienced gastrointestinal fistula, perforation, or abdominal abscess within the past 6 months;
• Has experienced hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York Class II or above), acute myocardial infarction, cerebral infarction, cerebral parenchymal hemorrhage, or other active cerebrovascular or cardiovascular diseases within the past 6 months;
• Patients with a history of arterial aneurysm or arteriovenous malformation;
• Having undergone major surgery within 28 days, or minor surgery or needle biopsy within 48 hours;
• Urinary protein 3-4+, or 24-hour urinary protein quantification\>1g;
• Simultaneously accompanied by serious and uncontrolled other diseases.

Sponsors & Collaborators

• Sun Yet-Sen University Cancer Center: lead

Study Sites (1)

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (19)

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Related Links

• National Comprehensive Cancer Network. (NCCN) Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer, Version 5. 2019.

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Hui Liu

CONTACT

02087343031; liuhui@sysucc.org.cn

Qiu Bo

CONTACT

02087343031; qiubo@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 10, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)