Targeted FSRT plus bevacizumab versus hippocampus-sparing whole-brain radiation for people with lung adenocarcinoma that has spread to the brain
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
This will test whether focused 5-day fractionated stereotactic radiotherapy (FSRT) combined with bevacizumab works better than hippocampus-avoidant whole-brain radiotherapy with a simultaneous boost at controlling brain metastases and protecting memory in adults with lung adenocarcinoma and extensive brain metastases.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 220 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Sun Yat-sen University Academic / other |
| Drugs / interventions | bevacizumab, radiation |
| Locations | 3 sites (Chongqing, Chongqing Municipality and 2 other locations) |
| Trial ID | NCT07481786 on ClinicalTrials.gov |
What this trial studies
This is an open-label, phase 3 randomized trial comparing two brain-directed approaches for adults with extensive brain metastases from lung adenocarcinoma. Participants are randomized 1:1 to receive either FSRT (30 Gy in 5 fractions) combined with intravenous bevacizumab every 3 weeks for four cycles, or hippocampus-avoidant whole-brain radiotherapy (25 Gy) with a simultaneous integrated boost to lesions (40 Gy total) over 10 fractions. The trial's main goals are to improve intracranial tumor control while preserving neurocognitive function, with secondary assessments of safety and overall outcomes. The study is conducted at Sun Yat-sen University Cancer Center and two affiliated hospitals in China.
Who should consider this trial
Good fit: Adults (≥18) with pathologically confirmed lung adenocarcinoma and extensive brain metastases per the trial definition (1–2 lesions with at least one ≥3 cm, or 3–10 with at least one ≥2 cm, or 11–20 lesions), with stable extracranial disease, ECOG 0–2, adequate organ function, and no prior brain radiotherapy.
Not a fit: Patients with leptomeningeal metastasis, uncontrolled extracranial disease, contraindications to bevacizumab (such as recent major bleeding or uncontrolled hypertension), prior brain radiotherapy, or urgent surgical mass effect are unlikely to benefit from enrollment.
Why it matters
Potential benefit: If successful, this approach could improve control of brain metastases while reducing memory and cognitive decline compared with standard hippocampus-sparing whole-brain radiation with a boost.
How similar studies have performed: A prior phase 2 study of FSRT combined with bevacizumab showed promising efficacy and safety, prompting this phase 3 comparison against hippocampus-avoidant WBRT with SIB.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Chongqing, Chongqing Municipality and 2 other locations
- The First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Recruiting)
- Sun yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine — Guangzhou, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: Hui Liu
- Email: liuhuisysucc@126.com
- Phone: 02087343031
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.