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

NCT ID: NCT06910761

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-05

Study Completion Date

2028-10-02

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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 Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and CSF sample collection

Craniospinal Irradiation

Intervention Type RADIATION

Undergo photon-VMAT-CSI

Electronic Health Record Review

Intervention Type OTHER

Ancillary studies

Lumbar Puncture

Intervention Type PROCEDURE

Undergo LP

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Ommaya Reservoir Tap

Intervention Type PROCEDURE

Undergo Ommaya reservoir tap

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Volume Modulated Arc Therapy

Intervention Type RADIATION

Undergo photon-VMAT-CSI

Interventions

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Biospecimen Collection

Undergo blood and CSF sample collection

Intervention Type PROCEDURE

Craniospinal Irradiation

Undergo photon-VMAT-CSI

Intervention Type RADIATION

Electronic Health Record Review

Ancillary studies

Intervention Type OTHER

Lumbar Puncture

Undergo LP

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Ommaya Reservoir Tap

Undergo Ommaya reservoir tap

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Volume Modulated Arc Therapy

Undergo photon-VMAT-CSI

Intervention Type RADIATION

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection LP Spinal Tap 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 Ommaya Reservoir Access VMAT Volumetric Modulated Arc Therapy (procedure)

Eligibility Criteria

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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 ≥ 60 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephanie M Yoon

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

City of Hope at Irvine Lennar

Irvine, California, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Stephanie M. Yoon

Role: primary

Stephanie M. Yoon

Role: primary

Other Identifiers

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NCI-2025-02015

Identifier Type: REGISTRY

Identifier Source: secondary_id

23911

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23911

Identifier Type: -

Identifier Source: org_study_id