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

NCT07789912 | Not Yet Recruiting Phase 2 DMC FDA Device

• 1 other identifier: 20260290
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leptomeningeal Metastasis; Breast Cancer; Lung Cancer (NSCLC)

Keywords

breast cancer; lung cancer; leptomeningeal metastasis; craniospinal irradiation

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 1.5 years

Secondary Outcomes (7)

• Overall Survival (OS) after brain-avoidant pCSI

  Up to 1.5 years

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

  Up to 1.5 years

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

  Up to 1.5 years

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

  3 months

• Patient-Reported Fatigue

  Up to 1.5 years

Study Arms (2)

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.

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.

Interventions

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.

Radiation Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis; Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Morgan Freret, MD

  University of Miami Miller School of Medicine-Sylvester Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Morgan Freret, MD

CONTACT

(305) 243-5470; mfreret@miami.edu

Markus Bredel, MD

CONTACT

(305) 243-4263; mbredel@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 27, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)