Recruiting
Phase 2

Photon-VMAT-CSI

Sponsor:

City of Hope Medical Center

Code:

NCT06910761

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Craniospinal Irradiation

Electronic Health Record Review

Lumbar Puncture

Magnetic Resonance Imaging

Study Details

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.

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

Study ID

NCT06910761

Start date

May 5, 2025

Status verified date

Nov, 2025

Completion date

Oct 2, 2028

Anticipated

Primary completion date

Oct 2, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

35 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

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

Biospecimen Collection

Undergo blood and CSF sample collection

Craniospinal Irradiation

Undergo photon-VMAT-CSI

Electronic Health Record Review

Ancillary studies

Lumbar Puncture

Undergo LP

Magnetic Resonance Imaging

Undergo MRI

Ommaya Reservoir Tap

Undergo Ommaya reservoir tap

Questionnaire Administration

Ancillary studies

Volume Modulated Arc Therapy

Undergo photon-VMAT-CSI

Primary outcome measure

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

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Stephanie M. Yoon

626-873-5241styoon@coh.org

Principal Investigator:

Stephanie M. Yoon

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Stephanie M. Yoon

626-873-5241styoon@coh.org

Principal Investigator:

Stephanie M. Yoon

More Information

Sponsor

City of Hope Medical Center

Last update posted

Dec 8, 2025

Last verified

Nov, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2025-12-08.