Phase III Trial of Brain MRI Surveillance in Stage IV Breast Cancer

This randomized, multi-institutional phase III trial evaluates whether routine surveillance brain MRI every 6 months improves detection and treatment characteristics of brain metastases in neurologically asymptomatic patients with stage IV breast cancer. Patients are stratified by receptor subtype, age, prior therapy, and study site, then randomized 1:1 to either scheduled surveillance MRIs or standard-of-care symptom-triggered imaging. The study aims to determine whether earlier detection leads to differences in treatment modality, frequency of brain metastases, leptomeningeal disease incidence, quality of life, and survival outcomes.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Surveillance Brain MRI; Diagnostic test: Standard of Care Brain Imaging

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rheese McNab; Phone Number: 813-745-1780; Email: Rheese.McNab@moffitt.org

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Not yet recruiting
      • Baptist Health South Florida
      • Principal Investigator: Rupesh Kotecha, MD
      • Principal Investigator: Reshma Mahtani, MD
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Kamran Ahmed, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic diagnosis of breast cancer with documentation of ER/PR/HER2 status
• Radiographic evidence of stage IV extracranial disease enrolled within 60 days of diagnosis or starting first line therapy. HR+/HER2- patients may be enrolled within 60 days of starting 2nd line therapy as well.
• HR+ will be defined as ER and/or PR > 10%. To be classified as HER2+ disease, overexpression of HER2 by either IHC or in-situ hybridization is necessary as defined by the ASCO / CAP Guidelines41. Triple negative will be classified as ER and PR <10% and HER2-.
• Age ≥ 18
• Life expectancy ≥ 6 months
• Eastern Cooperative Oncology Group performance status ≤ 2
• Patients must be able to understand and the willingness to sign an informed consent for study procedures
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• Prior diagnosis or treatment of brain metastases or leptomeningeal disease
• History of other non-breast malignancy requiring treatment with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of > 90%), such as but not limited to, non-melanoma skin cancers, stage I endometrioid uterine cancer, and others at the discretion of the PI
• Neurologic symptoms warranting standard screening brain MRI in the judgement of the treating physician at time of enrollment
• Indications warranting brain MRI for other neurologic conditions at time of study entry (including multiple sclerosis, stroke, traumatic brain injuries, epilepsy, hydrocephalus and pituitary gland disorders)
• Contraindication towards MRI with contrast
• Chronic kidney disease stage IV or V or end stage renal disease (CrCl <30 ml/min)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Surveillance Brain MRI; Participants receive a baseline brain MRI followed by surveillance brain MRI every 6 months for 24 months.	Diagnostic test: Surveillance Brain MRI; Routine scheduled MRI imaging at baseline and at 6-month intervals.
Other: Standard of Care Brain Imaging; Participants receive a baseline brain MRI followed by standard-of-care imaging only if neurologic symptoms develop.	Diagnostic test: Standard of Care Brain Imaging; Imaging performed only when clinically indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Characteristics of Brain Metastases	Proportion of patients receiving surgery or whole-brain radiation therapy for brain metastases.	Up to 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Brain Metastases	The frequency of metastasis detection over the 24-month screening/follow-up period.	Up to 24 Months
Leptomeningeal Disease Incidence	Incidence of radiographic detection of leptomeningeal disease.	Up to 24 Months
Brain Metastases at Diagnosis	Average number of lesions on diagnostic MRI.	Up to 24 Months
Size of Largest Brain Metastasis	Average size of largest brain metastasis.	Up to 24 Months
Overall Survival After Brain Metastasis Diagnosis	Time from brain metastasis diagnosis to death from any cause.	Up to 48 Months
Brain Metastasis Specific Survival	Time from brain metastasis diagnosis to death attributable to brain metastases.	Up to 48 Months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Florida Department of Health; Florida Biomedical Research Program - Bankhead Coley
• Investigators: Principal Investigator: Kamran Ahmed, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: MCC-24030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No