Clinical Trial Finder

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)

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.

Arms

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.

Interventions

Procedure: - Biospecimen Collection

Undergo blood and CSF sample collection

Radiation: - Craniospinal Irradiation

Undergo photon-VMAT-CSI

Other: - Electronic Health Record Review

Ancillary studies

Procedure: - Lumbar Puncture

Undergo LP

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Procedure: - Ommaya Reservoir Tap

Undergo Ommaya reservoir tap

Other: - Questionnaire Administration

Ancillary studies

Radiation: - Volume Modulated Arc Therapy

Undergo photon-VMAT-CSI