Leptomeningeal MetastasisBRAVO-LMNCT07789912
BRain-AVOidant Proton Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumor Malignancies
A study testing Radiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI) in people with Leptomeningeal Metastasis and Breast Cancer, run by University of Miami at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastasis, Breast Cancer, Lung Cancer (NSCLC)
- What is being tested?
- Radiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2026to 13 Oct 2030
- Phase
- Interventional
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
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Miami
Miami, Florida, 33136
Morgan Freret, MD, (305) 243-5470, mfreret@miami.edu
Markus Bredel, MD, (305) 243-4263, mbredel@miami.edu
About this study
Official 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)
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.
- Being tested
- Radiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI)
- Keywords
- breast cancer, lung cancer, leptomeningeal metastasis, craniospinal irradiation
- Medical subject headings
- Meningeal Carcinomatosis, Breast Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Radiation Treatment | Experimental | Participants in this group will undergo radiation treatments using brain-avoidant proton craniospinal irradiation (CSI). The prescribed radiation dose for all participants will be 30Gy (Cobalt Gray Equivalent [CGE]) in 10 fractions. Receives: Radiation: Radiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI) |
| Non-Interventional Arm | No intervention | Participants who decline BRAVO-pCSI will have the option to enroll in a non-interventional exploratory arm. Participants in this group will undergo the same baseline and follow-up assessments as participants receiving BRAVO-pCSI, including radiographic evaluations, cerebrospinal fluid (CSF) and serum assessments, neurocognitive testing, and quality-of-life assessments. No study intervention will be administered. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central Nervous System Progression Free Survival (CNS PFS)
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.
Measured: Up to 1.5 years
Secondary outcomes (12)
Overall Survival (OS) after brain-avoidant pCSI
Overall Survival (OS) is defined as the elapsed time from start of brain-avoidant pCSI until date of death from any cause.
Measured: Up to 1.5 years
Treatment Response Rate After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)
Response rate is defined as the proportion of participants showing best responses per Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria.
Measured: Up to 1.5 years
Evaluation of the Safety And Tolerability of Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)
Incidence of adverse events (AEs) and serious adverse events (SAEs) related to brain-avoidant pCSI, as assessed using the NCI CTCAE Version 5.0.
Measured: Up to 1.5 years
Rate of Cognitive Failure After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI)
Cognitive failure measured via the reliable change index (RCI) after BRAVO pCSI.
Measured: 3 months
Patient-Reported Depression
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.
Measured: Up to 1.5 years
Patient-Reported Fatigue
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.
Measured: Up to 1.5 years
Mean Symptom Severity Score (MDASI-BT)
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.
Measured: Up to 1.5 years
Mean Disease-Specific Symptom Score (MDASI-BT)
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.
Measured: Up to 1.5 years
Mean Symptom Interference Score (MDASI-BT)
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.
Measured: Up to 1.5 years
Mean Symptom Severity Score (MDASI-SP)
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.
Measured: Up to 1.5 years
Mean Disease-Specific Symptom Score (MDASI-SP)
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
Measured: Up to 1.5 years
Mean Symptom Interference Score (MDASI-SP)
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.
Measured: Up to 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2026
- Study start13 Oct 2026
- Primary completion13 Oct 2030 (estimated)
- Study completion13 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Morgan Freret, University of Miami
- Investigators
- Morgan Freret, MD, Principal investigator, University of Miami Miller School of Medicine-Sylvester Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07789912
- Sponsor's protocol ID
- 20260290
- Acronym
- BRAVO-LM
- Status last verified
- Oct 2026
- First submitted
- 24 Aug 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No