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

Phase II Trial of Photon Craniospinal Irradiation for Leptomeningeal Disease Secondary to Solid Tumor Malignancy

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Lung Non-Small Cell Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Metastatic Breast Carcinoma; Metastatic Malignant Neoplasm in the Leptomeninges
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Other: Electronic Health Record Review; Procedure: Lumbar Puncture; Procedure: Biospecimen Collection; Radiation: Craniospinal Irradiation; Procedure: Ommaya Reservoir Tap; Radiation: Volume Modulated Arc Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of photon-VMAT-CSI; assessed by median central nervous system progression free survival (CNS-PFS).

SECONDARY OBJECTIVES:

I. To estimate and assess central nervous system (CNS) response rate, response duration, and overall survival probability.

II. To summarize and assess toxicities including: type, frequency, severity, attribution, time course and duration.

III. To characterize and evaluate patient reported outcomes (PROs), including quality of life (QOL), measures:

IIIa. QOL Questionnaire Brain 20 (European Organization for Research and Treatment of Cancer [EORTC]-Quality of Life Questionnaire [QLQ]-Brain 20 [BN20]); IIIb. Core QOL Questionnaire 30 (EORTC-QLQ-Core 30 [C30]); IIIc. Patient reported outcomes measurement information system (PROMIS) for Anxiety; IIId. PROMIS Cognition.

EXPLORATORY OBJECTIVES:

I. To characterize inflammatory markers over time. II. To explore the potential association between inflammatory markers and radiation-related toxicity.

III. To evaluate the potential association between circulating cell-free deoxyribonucleic acid (cfDNA), imaging, and response.

IV. To evaluate possible genomic predictors of CNS progression.

OUTLINE:

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

After completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope at Irvine Lennar
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Photon-VMAT-CSI); 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.

Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Other: Electronic Health Record Review; Ancillary studies; Procedure: Lumbar Puncture; Undergo LP; Other Names: LP; Spinal Tap; Procedure: Biospecimen Collection; Undergo blood and CSF sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Craniospinal Irradiation; Undergo photon-VMAT-CSI; Procedure: Ommaya Reservoir Tap; Undergo Ommaya reservoir tap; Other Names: Ommaya Reservoir Access; Radiation: Volume Modulated Arc Therapy; Undergo photon-VMAT-CSI; Other Names: VMAT; Volumetric Modulated Arc Therapy (procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic response	Will be assessed per European Organization for Research and Treatment of Cancer (EORTC) Response Assessment in Neuro-Oncology. Will be characterized using a (generalized) linear mixed effects model.	Every 3 months after treatment until CNS disease progression or death, assessed up to 1 year
Quality of life	Will be assessed per EORTC Quality-of-Life Questionnaire Brain 20, EORTC Core Quality-of-Life Questionnaire 30, Patient Reported Outcome Measurement Information System (PROMIS) Anxiety short form and PROMIS Cognition short form. Will be characterized using a (generalized) linear mixed effects model.	At baseline, 1 month, and every 3 months until CNS disease progression or death, assessed up to 1 year
Incidence of adverse events	Will be assessed and graded according to the Common Terminology Criteria for Adverse Events version 5.0. Will be tabulated to show the number and percentage as well as the timing, severity, and attribution of the toxicity.	Up to 30 days after the last day of treatment
Overall 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 death (from any cause), or last contact, whichever occurs first, assessed up to 1 year

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephanie M Yoon, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): October 2, 2028
• Study Completion (Estimated): October 2, 2028

Study Registration Dates

• First Submitted: March 28, 2025
• First Submitted That Met QC Criteria: March 28, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Skin Diseases; Breast Diseases; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Skin and Connective Tissue Diseases; Lung Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Biopsy; Chemistry Techniques, Analytical; Spectrum Analysis; Radiotherapy; Diagnostic Techniques, Neurological; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Specimen Handling; Magnetic Resonance Spectroscopy; Spinal Puncture; Radiotherapy, Intensity-Modulated; Craniospinal Irradiation
• Other Study ID Numbers: 23911 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2025-02015 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No