Fractionated stereotactic radiotherapy plus bevacizumab for multiple brain metastases from lung adenocarcinoma

Fractionated Stereotactic Radiotherapy Combines With Bevacizumab for the Treatment of Multiple Brain Metastases in Lung Adenocarcinoma: a Prospective Controlled Phase III Study

This trial tests whether adding bevacizumab to fractionated stereotactic radiotherapy improves intracranial control for people with multiple brain metastases from lung adenocarcinoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 258 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: bevacizumab, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07058428 on ClinicalTrials.gov

What this trial studies

This is a prospective, controlled phase III randomized trial that will assign participants 1:1:1 to FSRT plus bevacizumab, FSRT alone, or whole-brain radiotherapy with a simultaneous integrated boost. FSRT is delivered as 30 Gy in five daily 6 Gy fractions, bevacizumab is given IV 7.5 mg/kg every three weeks for four cycles starting one week before FSRT, and WBRT/SIB is delivered as 25 Gy to the brain with a 40 Gy boost in 10 fractions. Eligible patients have lung adenocarcinoma with multiple brain metastases meeting predefined size/number criteria and are judged unsuitable for single-session SRS. The study will measure intracranial control and safety outcomes to determine whether the addition of bevacizumab provides clinical benefit.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed lung adenocarcinoma, 1–20 brain metastases meeting the trial's size criteria and deemed unsuitable for single-session SRS, with ECOG 0–2, stable extracranial disease, and adequate organ function are appropriate candidates.

Not a fit: Patients with uncontrolled extracranial disease, poor performance status (ECOG >2), contraindications to bevacizumab (for example recent major bleeding, poor wound healing), or those with lesions suitable for single-session SRS are less likely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase intracranial tumor control and reduce radiation-related edema, potentially improving neurological outcomes and prolonging survival.

How similar studies have performed: Prior studies show bevacizumab can reduce edema and improve radiotherapy effects in brain metastases, but large randomized phase III data specifically combining FSRT with bevacizumab for multiple brain metastases are limited.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Guangzhou, Guangdong

• Sun yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Hui Liu

Conditions Multiple Brain Metastases in Lung Adenocarcinoma