Breast Cancer, Leptomeningeal Metastasis, Lung Cancer (NSCLC)
Conditions
Keywords
breast cancer, lung cancer, leptomeningeal metastasis, craniospinal irradiation
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.
Interventions
RADIATIONRadiation Treatments Using Brain- Avoidant Proton Craniospinal Irradiation (BRAVO- pCSI)
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.
Sponsors
University of Miami
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Pathologically confirmed breast or non-small cell lung cancer (NSCLC) primary (group 1 and). Pathologically confirmed solid tumor malignancy (group 2). 3. Participants with adequate bone marrow function. 4. Participants with a Karnofsky Performance Status (KPS) ≥ 60. 5. Male and female participants ages ≥ 18 years. 6. Female participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method. 7. Male participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method.
Exclusion criteria
1. 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. 2. Participants with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy. 3. Participants with extensive systemic disease and without reasonable systemic treatment options. 4. Participants unable to undergo MRI brain and spine with gadolinium contrast. 5. 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. 6. Female participants who are pregnant or lactating. 7. Participants with impaired decision-making capacity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central Nervous System Progression Free Survival (CNS PFS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Symptom Severity Score (MDASI-SP) | 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. |
| Mean Disease-Specific Symptom Score (MDASI-SP) | 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 |
| Mean Symptom Interference Score (MDASI-SP) | 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. |
| Overall Survival (OS) after brain-avoidant pCSI | 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. |
| Treatment Response Rate After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI) | 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. |
| Evaluation of the Safety And Tolerability of Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI) | 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. |
| Rate of Cognitive Failure After Brain-Avoidant Proton Craniospinal Irradiation (BRAVO-pCSI) | 3 months | Cognitive failure measured via the reliable change index (RCI) after BRAVO pCSI. |
| Patient-Reported Depression | 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. |
| Patient-Reported Fatigue | 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. |
| Mean Symptom Severity Score (MDASI-BT) | 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. |
| Mean Symptom Interference Score (MDASI-BT) | 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. |
| Mean Disease-Specific Symptom Score (MDASI-BT) | 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. |
Countries
United States
Contacts
CONTACTMorgan Freret, MD
CONTACTMarkus Bredel, MD
PRINCIPAL_INVESTIGATORMorgan Freret, MD
University of Miami Miller School of Medicine-Sylvester Cancer Center
Outcome results
None listed