Photon Craniospinal Irradiation for the Treatment of Leptomeningeal Disease Secondary to Breast Cancer or Non-small Cell Lung Cancer

NCT06910761 | Recruiting Phase 2 DMC

• 3 other identifiers: 23911NCI-2025-02015P30CA033572
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well craniospinal irradiation (CSI) using photon volumetric modulated arc radiotherapy (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 and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal disease). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. 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. Photon-VMAT-CSI may be an effective treatment option for patients with leptomeningeal disease secondary to breast cancer or 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

  Will be estimated using the Kaplan-Meier estimator, and its associating 95% confidence limit will be calculated using the logit transformation and the Greenwood variance estimate.

  From start of treatment to CNS relapse, CNS progression, death (from any cause), or last contact, whichever occurs first, assessed up to 1 year

Secondary Outcomes (4)

• Radiographic response

  Every 3 months after treatment until CNS disease progression or death, assessed up to 1 year

• Quality of life

  At baseline, 1 month, and every 3 months until CNS disease progression or death, assessed up to 1 year

• Incidence of adverse events

  Up to 30 days after the last day of treatment

• Overall survival

  From start of treatment to death (from any cause), or last contact, whichever occurs first, assessed up to 1 year

Study Arms (1)

Treatment (Photon-VMAT-CSI)

EXPERIMENTAL

Patients undergo photon-VMAT-CSI QD for 10 treatments over 10-20 days (Monday-Friday) in the absence of disease progression or unacceptable toxicity. Patients undergo MRI during screening and follow-up and undergo collection of blood samples throughout the trial. Patients also undergo LP or Ommaya reservoir tap for CSF sample collection during screening and follow-up.

Procedure: Biospecimen Collection; Radiation: Craniospinal Irradiation; Other: Electronic Health Record Review; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Ommaya Reservoir Tap; Other: Questionnaire Administration; Radiation: Volume Modulated Arc Therapy

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and CSF sample collection

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

Treatment (Photon-VMAT-CSI)

Craniospinal Irradiation RADIATION

Undergo photon-VMAT-CSI

Treatment (Photon-VMAT-CSI)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (Photon-VMAT-CSI)

Lumbar Puncture PROCEDURE

Undergo LP

Also known as: LP, Spinal Tap

Treatment (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 (Photon-VMAT-CSI)

Ommaya Reservoir Tap PROCEDURE

Undergo Ommaya reservoir tap

Also known as: Ommaya Reservoir Access

Treatment (Photon-VMAT-CSI)

Questionnaire Administration OTHER

Ancillary studies

Treatment (Photon-VMAT-CSI)

Volume Modulated Arc Therapy RADIATION

Undergo photon-VMAT-CSI

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

Treatment (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:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• ≥ 18 years
• Karnofsky performance status (KPS) ≥ 60
• Ability to read and understand English or Spanish for questionnaires, or ability to complete questionnaires using certified interpreter
• Histologically confirmed breast cancer or non-small cell lung cancer
• Leptomeningeal disease established either radiographically and/or CSF cytology
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• Hemoglobin ≥ 8 g/dL
• Platelet ≥ 100,000/mm\^3
• Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 month after the last dose of protocol therapy
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

You may not qualify if:

• Chemotherapy, biological therapy, immunotherapy within 7 days prior to day 1 of protocol therapy
• Any prior radiation that in the opinion of the investigator unable to respect normal tissue tolerances and preclude craniospinal irradiation
• Patients with multiple or serious major neurologic symptoms (including encephalopathy) per physician / investigator assessment
• Patients with extensive, uncontrolled extracranial systemic disease
• Patients without reasonable systemic treatment options per physician / investigator
• Other clinically significant uncontrolled illness per opinion of physician / investigator
• Patients with a history or evidence of HIV infection (unless on effective anti-retroviral therapy with undetectable viral load based on prior tests within 6 months are eligible for this trial)
• Patients with history or evidence of chronic hepatitis B virus (HBV) infection (unless HBV viral load is undetectable based on prior tests and on suppressive therapy)
• Patients with a history or evidence of hepatitis C virus (HCV) infection unless treated and cured. (Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load based on prior tests)
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study are eligible for this trial
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Unable to undergo MRI brain and spine with gadolinium contrast
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

MeSH Terms

Conditions

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

Interventions

Specimen Handling; Craniospinal Irradiation; 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; Radiotherapy; Therapeutics; Biopsy; Diagnostic Techniques, Neurological; Punctures; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• Stephanie M Yoon

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

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: March 28, 2025
• First Posted: April 4, 2025
• Study Start: May 5, 2025
• Primary Completion (Estimated): October 2, 2028
• Study Completion (Estimated): October 2, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-11

Locations

US (2)