NCT07481786

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Background Brain metastases represent a severe complication of lung adenocarcinoma, significantly impairing both survival and quality of life. For patients with multiple or large brain metastases who are not candidates for stereotactic radiosurgery (SRS), hippocampus-avoidant whole-brain radiotherapy is considered a standard treatment option. However, this approach is limited by residual neurocognitive decline and suboptimal intracranial disease control. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, has been shown to normalize tumor vasculature, enhance radiation sensitivity, reduce cerebral edema, and lower the risk of radiation-induced brain necrosis. Fractionated stereotactic radiotherapy (FSRT) offers effective local control with reduced toxicity compared to single-session SRS. A prior phase 2 study demonstrated promising efficacy and safety of FSRT combined with bevacizumab in this patient population. The present phase 3 trial aims to test the hypothesis that FSRT plus bevacizumab (FSRT-Bev) improves intracranial control and reduces neurocognitive toxicity compared to hippocampus-avoidant whole-brain radiotherapy with simultaneous integrated boost (HA-WBRT-SIB). Study Design This is a prospective, open-label, phase 3 randomized controlled trial being conducted at Sun Yat-sen University Cancer Center. Patients are randomized in a 1:1 ratio to one of two treatment arms: Arm A (Experimental): FSRT combined with bevacizumab; Arm B (Control): HA-WBRT with SIB Treatment Interventions Arm A: FSRT is delivered to the gross tumor volume (GTV) at a total dose of 30 Gy in 5 daily fractions (6 Gy per fraction) using image-guided radiotherapy (IGRT). Bevacizumab is administered intravenously at a dose of 7.5 mg/kg every 3 weeks for 4 cycles, beginning one week prior to the start of FSRT. Arm B: Hippocampus-avoidant whole-brain radiotherapy is delivered at a dose of 25 Gy in 10 daily fractions, with a simultaneous integrated boost (SIB) to gross metastatic lesions up to 40 Gy in 10 fractions. Co-Primary Endpoints 1. Intracranial Progression-Free Survival (IPFS): Defined as the time of randomization to the first intracranial progression or death. 2. Neurocognitive failure Rate at 6 Months Post-Radiotherapy: Assessed using the reliable change index (RCI) based on validated neurocognitive tests, including the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association Test (COWA), and Trail Making Test Parts A and B (TMT-A, TMT-B).

Conditions

• Lung Adenocarcinoma
• Brain Metastases
• Radiotherapy, Intensity-Modulated
• Bevacizumab
• Whole-Brain Radiotherapy

Interventions

Type	Name	Description
RADIATION	FSRT	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).
RADIATION	HA-WBRT-SIB	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.
DRUG	Bevacizumab	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.

Timeline

• Start date: 2026-03-20
• Primary completion: 2029-09-15
• Completion: 2029-09-15
• First posted: 2026-03-19
• Last updated: 2026-04-06

Locations

3 sites across 1 country: China