Hippocampal Avoidance in Craniospinal Irradiation for the Treatment of Leptomeningeal Metastases From Breast Cancer or Non-small Cell Lung Cancer

NCT06518057 | Recruiting Phase 2 DMC FDA Device

• 3 other identifiers: RG1124476NCI-2024-05661FHIRB0020569
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Neoplasm in the Leptomeninges; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Central nervous system (CNS)-progression free survival (PFS)

  PFS is defined as time from craniospinal irradiation (CSI) to CNS disease progression or death. CNS-PFS will be summarized using Kaplan-Meier methodology. Median, 95% confidence interval (CI) and Kaplan-Meier plot will be provided. One-sample log-rank test will be used to test if the median CNS PFS of hippocampal avoidance in CSI for leptomeningeal metastases from breast cancer or non-small cell lung cancer (NSCLC) is significantly larger than the expected median CNS PFS with involved-field radiation therapy (IFRT), i.e., 2.5 months. P-value will be provided.

  Up to 12 months

Secondary Outcomes (3)

• Number of adverse events associated with hippocampal avoidance craniospinal irradiation (HA-CSI)

  Up to 12 months

• Neurocognitive function assessment

  Up to 12 months

• Overall survival (OS)

  Up to 12 months

Study Arms (1)

Treatment (Proton or Photon VMAT CSI)

EXPERIMENTAL

Patients undergo proton or photon VMAT CSI with HA over approximately 45 minutes once daily (QD) for 10 days (Monday-Friday) in the absence of unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening. Additionally, patients undergo additional CT for radiation planning during screening and magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo lumbar puncture (LP) or alternative methods for cerebral spinal fluid (CSF) collection at the discretion of the treating physician and principal investigator throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Electronic Health Record Review; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Proton Beam Craniospinal Irradiation; Other: Survey Administration; Radiation: Volume Modulated Arc Therapy; Procedure: Hippocampal-Avoidance Craniospinal Irradiation

Interventions

Biospecimen Collection PROCEDURE

Undergo CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Proton or Photon VMAT CSI)

Computed Tomography PROCEDURE

Undergo PET/CT and/or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (Proton or Photon VMAT CSI)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (Proton or Photon VMAT CSI)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (Proton or Photon VMAT CSI)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (Proton or Photon VMAT CSI)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (Proton or Photon VMAT CSI)

Proton Beam Craniospinal Irradiation RADIATION

Undergo proton CSI

Also known as: Craniospinal Proton Beam Radiation Therapy, p-CSI, Proton Craniospinal Irradiation, Proton Craniospinal Radiation Therapy

Treatment (Proton or Photon VMAT CSI)

Survey Administration OTHER

Ancillary studies

Treatment (Proton or Photon VMAT CSI)

Volume Modulated Arc Therapy RADIATION

Undergo photon VMAT CSI

Also known as: VMAT, Volumetric Modulated Arc Therapy (procedure)

Treatment (Proton or Photon VMAT CSI)

Hippocampal-Avoidance Craniospinal Irradiation PROCEDURE

Undergo HA

Also known as: Hippocampal-sparing Craniospinal Irradiation

Treatment (Proton or Photon VMAT CSI)

Eligibility Criteria

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

You may qualify if:

• Patients with breast cancer or NSCLC malignancies with leptomeningeal metastases established radiographically and/or through CSF cytology
• Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases
• Patients ≥ 18 years old
• Karnofsky performance status (KPS) ≥ 60 or Eastern Cooperative Oncology Group (ECOG) ≥ 2
• The patient is able to provide informed consent
• Hemoglobin \> 8 g/dL
• Absolute neutrophil count \> 1,000/mm
• Platelet count \> 100,000/mm
• Participants born female at birth must either be of non-reproductive potential (i.e. post-menopausal by history \[≥ 60 years old, or with no menses for \> 1 year without an alternative medical cause\], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum /urine pregnancy test within 3 weeks prior to starting radiation therapy (RT)
• Patients with reproductive potential must agree to practice two highly effective contraceptive methods

You may not qualify if:

• Patients with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy
• Patients with extensive systemic disease and without reasonable systemic treatment options
• Patients who are unable to undergo MRI brain and spine with gadolinium contrast
• Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances
• Gross ventricular disease
• Brain metastases within 5 mm of the hippocampal contours not previously treated
• Pregnant or lactating women

Sponsors & Collaborators

• University of Washington: lead

Study Sites (2)

University of California San Francisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

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

Interventions

Specimen Handling; Spinal Puncture; Magnetic Resonance Spectroscopy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy

Study Officials

• Lia M. Halasz

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lia M. Halasz

CONTACT

206-897-2121; lhalasz@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: July 24, 2024
• Study Start: March 3, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)