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

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.

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)