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Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases

RECRUITINGPhase 3Sponsored by Sun Yat-sen University
Actively Recruiting
PhasePhase 3
SponsorSun Yat-sen University
Started2026-03-20
Est. completion2029-09-15
Eligibility
Age18 Years+
Healthy vol.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.

Eligibility

Age: 18 Years+Healthy volunteers accepted
Inclusion Criteria:

* Age ≥18 years
* Pathologically confirmed non-squamous non-small cell lung cancer (adenocarcinoma)
* Extensive brain metastases meeting any of the following:

1-2 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 Criteria:

* 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

Conditions7

BevacizumabBrain MetastasesCancerLung AdenocarcinomaLung CancerRadiotherapy, Intensity-ModulatedWhole-Brain Radiotherapy

Interventions1

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