Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
Application of Bevacizumab Combined With Fractionated Stereotactic Radiotherapy (FSRT-Bev) Versus Hippocampus-Avoidant Whole-Brain Radiotherapy With Simultaneous Integrated Boost (HA-WBRT-SIB) in Patients With Extensive Brain Metastases From Lung Adenocarcinoma: A Phase III Randomized Controlled Trial Evaluating Intracranial Control Efficacy and Neurocognitive Function
Sun Yat-sen University
220 participants
Mar 20, 2026
INTERVENTIONAL
Conditions
Summary
This is a phase 3, randomized, controlled clinical trial comparing two brain-directed treatment strategies for adult patients with extensive brain metastases from lung adenocarcinoma. The trial compares fractionated stereotactic radiotherapy combined with bevacizumab (FSRT-Bev) versus hippocampus-avoidant whole-brain radiotherapy with simultaneous integrated boost (HA-WBRT-SIB). The main objectives are to evaluate intracranial tumor control and preservation of neurocognitive function . Patients will be randomly assigned in a 1:1 ratio to receive either FSRT plus bevacizumab or HA-WBRT-SIB. In the experimental group, FSRT is delivered to visible brain tumors over 5 daily treatments (total 30 Gy, 6 Gy per fraction). Bevacizumab is given intravenously every 3 weeks for 4 cycles. In the control group, patients receive hippocampus-avoidant whole-brain radiation (25 Gy) with a simultaneous dose boost to metastatic lesions (40 Gy total) over 10 daily treatments.
Eligibility
Inclusion Criteria8
- Age ≥18 years
- Pathologically confirmed non-squamous non-small cell lung cancer (adenocarcinoma)
- Extensive brain metastases meeting any of the following:
- -2 metastases with at least one ≥3 cm in diameter; or 3-10 metastases with at least one ≥2 cm; or 11-20 metastases
- Stable extracranial disease
- ECOG performance status 0-2
- Adequate bone marrow, hepatic, and renal function
- Written informed consent
Exclusion Criteria9
- Contraindications to bevacizumab (uncontrolled hypertension, history of bleeding/thromboembolism, recent surgery, etc.)
- Leptomeningeal metastasis
- Prior brain radiotherapy or surgical resection of brain metastases
- Significant mass effect requiring urgent neurosurgical intervention
- Severe cardiovascular, vascular, or gastrointestinal disease within 6 months
- Proteinuria ≥3+ or 24-hour urine protein >1 g
- Other active malignancies (except curable non-melanoma skin cancer or cervical carcinoma in situ)
- Inability to comply with neurocognitive testing
- Pregnancy or breastfeeding
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Interventions
The FSRT-bevacizumab group receives FSRT plus bevacizumab. FSRT targets visible intracranial lesions, with a total dose of 30 Gy administered once daily for 5 fractions (6 Gy per fraction).
The HA-WBRT-SIB group receives whole-brain radiotherapy with hippocampal avoidance and a simultaneous integrated boost (SIB) to visible intracranial lesions. A total dose of 25 Gy is delivered to the whole brain, while visible lesions are simultaneously boosted to 40 Gy. Treatment is administered once daily for a total of 10 fractions.
Bevacizumab is initiated one week before the start of FSRT and administered every 3 weeks for a total of 4 cycles, via intravenous injection at a dose of 7.5 mg/kg.
Locations(3)
View Full Details on ClinicalTrials.gov
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NCT07481786