Recruiting
Phase 2

Hippocampal Avoidance

Sponsor:

University of Washington

Code:

NCT06518057

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Electronic Health Record Review

Lumbar Puncture

Magnetic Resonance Imaging

Study Details

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

Study ID

NCT06518057

Start date

Mar 3, 2025

Status verified date

Jun, 2026

Completion date

Jul 1, 2028

Anticipated

Primary completion date

Jul 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

22 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (Proton or Photon VMAT CSI)

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.

Interventions

Biospecimen Collection

Undergo CSF sample collection

Computed Tomography

Undergo PET/CT and/or CT

Electronic Health Record Review

Ancillary studies

Lumbar Puncture

Undergo lumbar puncture

Magnetic Resonance Imaging

Undergo MRI

Positron Emission Tomography

Undergo PET/CT

Proton Beam Craniospinal Irradiation

Undergo proton CSI

Survey Administration

Ancillary studies

Volume Modulated Arc Therapy

Undergo photon VMAT CSI

Hippocampal-Avoidance Craniospinal Irradiation

Undergo HA

Primary outcome measure

  • Central nervous system (CNS)-progression free survival (PFS) [ Time Frame: Up to 12 months ]

Central Contacts and Locations

Central contacts

Lia M. Halasz

206-897-2121lhalasz@uw.edu

Locations

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Jonathan Yang

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Lia M. Halasz

206-897-2121lhalasz@uw.edu

Principal Investigator:

Lia M. Halasz

More Information

Sponsor

University of Washington

Last update posted

Aug 14, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by University of Washington on 2026-08-14.