Skip to main content
OpenTrials
Not yet recruiting

NCT Number: NCT07789912

BRain-AVOidant Proton Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumor Malignancies

The purpose of this study is to determine the efficacy of BRain-AVOidant proton craniospinal irradiation (BRAVO pCSI) in adult participants with leptomeningeal metastases from solid tumors.

Not yet recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Leptomeningeal Metastasis Breast Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Central Nervous System Neoplasms Lung Cancer (NSCLC) Lung Diseases Lung Neoplasms Meningeal Carcinomatosis Meningeal Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with leptomeningeal metastases established radiographically and/or through Cerebrospinal Fluid (CSF) cytology or circulating tumor cells (CTCs). Participants may have newly diagnosed or recurrent LM.
  • Pathologically confirmed breast or non-small cell lung cancer (NSCLC) primary (group 1 and). Pathologically confirmed solid tumor malignancy (group 2).
  • Participants with adequate bone marrow function.
  • Participants with a Karnofsky Performance Status (KPS) ≥ 60.
  • Male and female participants ages ≥ 18 years.
  • Female participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method.
  • Male participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method.

Exclusion criteria

  • Participants with metastases within the memory-avoidance structures (hippocampus, corpus callosum, fornix, amygdala) that preclude developing a treatment plan that respects dosimetric constraints for these structures.
  • Participants with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy.
  • Participants with extensive systemic disease and without reasonable systemic treatment options.
  • Participants unable to undergo MRI brain and spine with gadolinium contrast.
  • Participants who have had radiation therapy to the spinal cord with equivalent dose in 2Gy fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using α/β of 3.
  • Female participants who are pregnant or lactating.
  • Participants with impaired decision-making capacity.

Treatment and study plan

Radiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI)

Radiation

Participants with Leptomeningeal Metastases (LM) from breast or non-small cell lung cancer will be included in Group 1 (20 evaluable participants). Participants with LM from solid tumors of other histologies will be included in Group 2 (10 evaluable participants). All participants in Groups 1 and 2 will receive Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI) at a prescribed dose of 30 Gy (Cobalt Gray Equivalent [CGE]) delivered in 10 fractions.

Protocol treatment must begin within 21 days of study enrollment and will be delivered over approximately 2 weeks.

Primary outcomes

  1. Central Nervous System Progression Free Survival (CNS PFS)

    Time frame: Up to 1.5 years

    Central Nervous System Progression Free Survival (CNS PFS) is defined as the elapsed time from start of brain-avoidant pCSI until the date of first event of CNS disease progression or death.

Secondary outcomes

  1. Overall Survival (OS) after brain-avoidant pCSI

    Time frame: Up to 1.5 years

    Overall Survival (OS) is defined as the elapsed time from start of brain-avoidant pCSI until date of death from any cause.

  2. Treatment Response Rate After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)

    Time frame: Up to 1.5 years

    Response rate is defined as the proportion of participants showing best responses per Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria.

  3. Evaluation of the Safety And Tolerability of Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)

    Time frame: Up to 1.5 years

    Incidence of adverse events (AEs) and serious adverse events (SAEs) related to brain-avoidant pCSI, as assessed using the NCI CTCAE Version 5.0.

  4. Rate of Cognitive Failure After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)

    Time frame: 3 months

    Cognitive failure measured via the reliable change index (RCI) after BRAVO pCSI.

  5. Patient-Reported Depression

    Time frame: Up to 1.5 years

    Depression will be assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Total scores range from 0 to 60, with higher scores indicating greater depressive symptoms.

  6. Patient-Reported Fatigue

    Time frame: Up to 1.5 years

    Fatigue will be assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale Version 4 (Items 1-13). Total scores range from from 0 to 52, with higher scores indicating less fatigue.

  7. Mean Symptom Severity Score (MDASI-BT)

    Time frame: Up to 1.5 years

    Mean score on the symptom severity subscale of the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Scores range from 0 to 10, with higher scores indicating greater symptom severity.

  8. Mean Disease-Specific Symptom Score (MDASI-BT)

    Time frame: Up to 1.5 years

    Mean score on the brain tumor-specific symptom subscale of the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Scores range from 0 to 10, with higher scores indicating greater symptom burden.

  9. Mean Symptom Interference Score (MDASI-BT)

    Time frame: Up to 1.5 years

    Mean score on the symptom interference subscale of the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Scores range from 0 to 10, with higher scores indicating greater symptom interference.

  10. Mean Symptom Severity Score (MDASI-SP)

    Time frame: Up to 1.5 years

    Mean score on the symptom severity subscale of the MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP). Scores range from 0 to 10, with higher scores indicating greater symptom severity.

  11. Mean Disease-Specific Symptom Score (MDASI-SP)

    Time frame: Up to 1.5 years

    Mean score on the spine tumor-specific symptom subscale of the MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP). Scores range from 0 to 10, with higher scores indicating greater symptom burden

  12. Mean Symptom Interference Score (MDASI-SP)

    Time frame: Up to 1.5 years

    Mean score on the symptom interference subscale of the MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP). Scores range from 0 to 10, with higher scores indicating greater symptom interference.

Study contacts

Contact information is provided by the study sponsor or research team.

Markus Bredel, MD

CONTACT

[email protected]

(305) 243-4263

Morgan Freret, MD

CONTACT

[email protected]

(305) 243-5470

Sponsors and collaborators

Lead sponsor

University of Miami

Other

Registry information

Official study title

A Phase II Study Assessing the Efficacy of BRain-AVOidant Proton Craniospinal Irradiation (CSI) for Leptomeningeal Metastases (LM) From Solid Tumor Malignancies (BRAVO-LM)

Acronym: BRAVO-LM

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Aug 27, 2026
Registry last updated
Sep 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.