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

City of Hope

Status and phase

Enrolling

Phase 2

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Metastatic Breast Carcinoma

Metastatic Lung Non-Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Metastatic Malignant Neoplasm in the Leptomeninges

Treatments

Radiation: Craniospinal Irradiation

Radiation: Volume Modulated Arc Therapy

Other: Questionnaire Administration

Procedure: Ommaya Reservoir Tap

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Procedure: Lumbar Puncture

Other: Electronic Health Record Review

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06910761

P30CA033572 (U.S. NIH Grant/Contract)

23911

NCI-2025-02015 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

35 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

35 participants in 1 patient group

Treatment (Photon-VMAT-CSI)

Experimental group

Description:

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.

Treatment: