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

Phase 2

Recruiting

• 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

• Registration Number: NCT06910761
• Lead Sponsor: City of Hope Medical Center

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.

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 Timeline

• Study First Submitted: 2025-03-28
• Study First Submitted QC: 2025-03-28
• Study First Posted: 2025-04-04
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-18
• Last Update Posted: 2025-06-24
• Study Start: 2025-09-24
• Primary Completion: 2028-10-02
• Study Completion: 2028-10-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Central nervous system (CNS)-progression free survival	From start of treatment to CNS relapse, CNS progression, death (from any cause), or last contact, whichever occurs first, assessed up to 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Radiographic response	Every 3 months after treatment until CNS disease progression or death, assessed up to 1 year	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.
Quality of life	At baseline, 1 month, and every 3 months until CNS disease progression or death, assessed up to 1 year	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.
Incidence of adverse events	Up to 30 days after the last day of treatment	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.
Overall survival	From start of treatment to death (from any cause), or last contact, whichever occurs first, assessed up to 1 year	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.

Trial Locations

Locations (2)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

City of Hope at Irvine Lennar; 🇺🇸 Irvine, California, United States