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

NCT07481786 | Not Yet Recruiting Phase 3

• 1 other identifier: 2025-FXY-308
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

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

Keywords

Lung Adenocarcinoma; Brain Metastases; fractionated stereotactic radiotherapy (FSRT); Bevacizumab; Whole-brain radiotherapy with simultaneous integrated boost (HA-WBRT-SIB)

Outcome Measures

Primary Outcomes (2)

• Intracranial Progression-Free Survival (IPFS)

  Defined as the time from randomization to the first documentation of intracranial progression, death, or last follow-up.

  18 months

• Neurocognitive Function failure

  Neurocognitive failure is the first failure, defined as a neurocognitive decline using the reliable change index (RCI) on at least one of the following assessments: HVLT-R, TMT, or COWA

  6 months

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  18 months

• Overall Survival (OS)

  18 months

• Quality of Life Assessment

  18 months

• Safety Assessment

  18 months

Study Arms (2)

The FSRT-beva group

EXPERIMENTAL

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). 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.

Radiation: FSRT; Drug: Bevacizumab

The HA-WBRT-SIB group

ACTIVE COMPARATOR

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.

Radiation: HA-WBRT-SIB

Interventions

FSRT RADIATION

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 FSRT-beva group

HA-WBRT-SIB RADIATION

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.

The HA-WBRT-SIB group

Bevacizumab DRUG

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.

The FSRT-beva group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

The First Affiliated Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, 510405, China

Location

Related Publications (12)

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• Westover KD, Mendel JT, Dan T, Kumar K, Gao A, Pulipparacharuv S, Iyengar P, Nedzi L, Hannan R, Anderson J, Choe KS, Jiang W, Abdulrahman R, Rahimi A, Folkert M, Laine A, Presley C, Cullum CM, Choy H, Ahn C, Timmerman R. Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer. Neuro Oncol. 2020 Dec 18;22(12):1831-1839. doi: 10.1093/neuonc/noaa092.

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• Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27.

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• Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.

  PMID: 16757720 RESULT

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  PMID: 16856022 RESULT

• Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149.

  PMID: 15254054 RESULT

MeSH Terms

Conditions

Adenocarcinoma of Lung; Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Hui Liu

CONTACT

02087343031; liuhuisysucc@126.com

Bo Qiu

CONTACT

02087343031

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professer

Study Record Dates

• First Submitted: March 15, 2026
• First Posted: March 19, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): September 15, 2029
• Study Completion (Estimated): September 15, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)