Photon VMAT craniospinal radiation for leptomeningeal disease from breast or non‑small cell lung cancer
Phase II Trial of Photon Craniospinal Irradiation for Leptomeningeal Disease Secondary to Solid Tumor Malignancy
This trial tests whether craniospinal irradiation delivered with photon VMAT can help adults whose breast cancer or non‑small cell lung cancer has spread to the meninges (leptomeningeal disease).
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 35 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | Chemotherapy, immunotherapy, radiation |
| Locations | 2 sites (Duarte, California and 1 other locations) |
| Trial ID | NCT06910761 on ClinicalTrials.gov |
What this trial studies
This Phase II trial delivers photon volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) once daily for 10 treatments over 10–20 days to patients with leptomeningeal disease secondary to breast cancer or non‑small cell lung cancer. The main goal is to measure central nervous system progression‑free survival (CNS‑PFS), with secondary endpoints including CNS response rate, duration of response, overall survival, treatment toxicities, and patient‑reported quality of life. Participants undergo baseline and follow‑up brain/spine MRI, lumbar punctures and biospecimen collection for exploratory correlative studies of inflammatory markers, circulating cfDNA, and genomic predictors. Safety and symptom effects will be tracked closely alongside imaging and patient‑reported outcomes.
Who should consider this trial
Good fit: Adults (≥18) with histologically confirmed breast cancer or non‑small cell lung cancer and radiographic or CSF‑confirmed leptomeningeal disease, KPS ≥60, adequate blood counts and organ function, and ability to complete questionnaires are eligible.
Not a fit: Patients with poor performance status (KPS <60), extensive uncontrolled systemic disease, or medical contraindications to craniospinal radiotherapy are unlikely to benefit from this treatment.
Why it matters
Potential benefit: If successful, this approach could extend the time without CNS progression and reduce neurologic symptoms by targeting disease throughout the brain and spinal canal.
How similar studies have performed: Conventional craniospinal irradiation has provided symptom control in some prior reports, but photon‑VMAT CSI as a modern, targeted delivery method is still investigational and not yet proven in this setting.
Eligibility criteria
Show full inclusion / exclusion criteria
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)
Where this trial is running
Duarte, California and 1 other locations
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
- City of Hope at Irvine Lennar — Irvine, California, United States (Recruiting)
Study contacts
- Principal investigator: Stephanie M Yoon — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.