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Lung AdenocarcinomaPhase 3NCT07481786

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

A Phase 3 study testing FSRT, HA-WBRT-SIB and Bevacizumab in people with Lung Adenocarcinoma and Brain Metastases, run by Sun Yat-sen University at 3 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
FSRT, HA-WBRT-SIB and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
220 participants
Where
3 sitesChina
Study dates
20 Mar 2026to 15 Sep 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Other active malignancies (except curable non-melanoma skin cancer or cervical carcinoma in situ)
  • Inability to comply with neurocognitive testing
  • Pregnancy or breastfeeding

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Hui Liu contact

02087343031

liuhuisysucc@126.com

Bo Qiu contact

02087343031

China3 sites, 3 recruiting

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 400016

    Rui Zhou, Doctor, tumorrui@163.com

    Recruiting

  • Sun yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Hui Liu, 86-020-87343031, liuhuisysucc@126.com

    Recruiting

  • The First Affiliated Hospital of Guangzhou University of Chinese Medicine

    Guangzhou, Guangdong, 510405

    Linzhu Zhai, Doctor, 86-020-36492585, linzhuzhai@163.com

    Recruiting

Other trials in China

About this study

Official title: 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 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.

Read the 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).
Being tested
FSRT, HA-WBRT-SIB, Bevacizumab
Keywords
Lung Adenocarcinoma, Brain Metastases, fractionated stereotactic radiotherapy (FSRT), Bevacizumab, Whole-brain radiotherapy with simultaneous integrated boost (HA-WBRT-SIB)
Medical subject headings
Adenocarcinoma of Lung, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FSRTRadiation

    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).

  • HA-WBRT-SIBRadiation

    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.

  • BevacizumabDrug

    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.

Study groups in NCT07481786
Study groupRoleWhat they receive
The FSRT-beva groupExperimentalThe 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.
Receives: Radiation: FSRT; Drug: Bevacizumab
The HA-WBRT-SIB groupActive comparatorThe 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.
Receives: Radiation: HA-WBRT-SIB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial Progression-Free Survival (IPFS)

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

    Measured: 18 months

  2. 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

    Measured: 6 months

Secondary outcomes (4)

  1. Progression-Free Survival (PFS)

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

    Measured: 18 months

  2. Overall Survival (OS)

    Defined as the time of randomization to death or last follow-up.

    Measured: 18 months

  3. Quality of Life Assessment

    Quality of life (QoL) is assessed at baseline and at 2, 6, and 12 months after radiotherapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), version 3.0.

    Measured: 18 months

  4. Safety Assessment

    Safety is assessed by monitoring adverse events (graded by CTCAE), laboratory tests, neurological toxicity, and radiation-induced brain necrosis. All treatment-related toxicities are documented and analyzed for severity and clinical significance.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2026
  2. Study start20 Mar 2026
  3. Primary completion15 Sep 2029 (estimated)
  4. Study completion15 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
220 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07481786
Sponsor's protocol ID
2025-FXY-308
Status last verified
Apr 2026
First submitted
15 Mar 2026
Last updated
6 Apr 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol. 2013 Sep;15(9):1257-63. doi: 10.1093/neuonc/not085. Epub 2013 Jun 27.

    PubMed 23814264

  • Xiangying M, Rugang Z, Lijuan D, Yaowei Z, Bing S, Junliang W, Dan L, Shikai W. Low-dose bevacizumab as an effective pre-treatment for peri-tumoral brain edema prior to CyberKnife radiosurgery: A case report. Cancer Biol Ther. 2018 Jun 3;19(6):461-464. doi: 10.1080/15384047.2018.1433499. Epub 2018 Mar 21.

    PubMed 29420112

  • Lehrer EJ, Peterson JL, Zaorsky NG, Brown PD, Sahgal A, Chiang VL, Chao ST, Sheehan JP, Trifiletti DM. Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials. Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):618-630. doi: 10.1016/j.ijrobp.2018.10.038. Epub 2018 Nov 2.

    PubMed 30395902

  • Jiang T, Zhang Y, Li X, Zhao C, Chen X, Su C, Ren S, Yang N, Zhou C. EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in patients with EGFR-mutant NSCLC and multiple brain metastases. Eur J Cancer. 2019 Nov;121:98-108. doi: 10.1016/j.ejca.2019.08.021. Epub 2019 Sep 27.

    PubMed 31569068

  • 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.

    PubMed 32347302

  • Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029. doi: 10.1200/JCO.19.02767. Epub 2020 Feb 14.

    PubMed 32058845

  • 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.

    PubMed 25349290

  • 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.

    PubMed 16757720

  • Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.

    PubMed 19801201

  • Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.

    PubMed 27458945

  • Tsao MN, Lloyd N, Wong R, Chow E, Rakovitch E, Laperriere N. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD003869. doi: 10.1002/14651858.CD003869.pub2.

    PubMed 16856022

  • 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.

    PubMed 15254054

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing FSRT, HA-WBRT-SIB and Bevacizumab in people with Lung Adenocarcinoma and Brain Metastases, run by Sun Yat-sen University at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Hui Liu (02087343031, liuhuisysucc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Progression-Free Survival (IPFS) (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07481786, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.

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