An Investigational Scan (64Cu-DOTA-Trastuzumab PET/MRI) in Imaging Patients With HER2+ Breast Cancer With Brain Metastasis

PRIMARY OBJECTIVES:

I. Evaluate the feasibility of 64Cu-DOTA-trastuzumab PET imaging in patients with HER2+ breast cancer metastatic to the brain.

II. Evaluate if HER2+ breast cancer patients with brain metastasis who are responders to fam-trastuzumab deruxtecan have higher maximum standardized uptake value (SUVmax) (minimum over all lesions in the brain) than non-responders.

SECONDARY OBJECTIVE:

I. Evaluate if the minimum SUVmax of all quantifiable lesions in a given patient is associated with time to progression in the brain.

OUTLINE:

Patients receive trastuzumab intravenously (IV) over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.

Inclusion criteria

• Documented informed consent of the participant and/or legally authorized representative
• Women with documented metastatic HER2 positive breast cancer (American Society of Clinical Oncology [ASCO] College of American Pathologist [CAP] guidelines) who have brain metastases
• Age > 18 years
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Patients with leptomeningeal disease will be considered eligible
• Planned therapy with fam-trastuzumab deruxtecan
• Left ventricular ejection fraction (LVEF) > 50%
• Absolute neutrophil count (ANC) > 1.5 x 10^9/L
• Platelets > 100 x 10^9/L
• Hemoglobin > 9 g/dL
• Total (T.) bilirubin < 3 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN
• Creatinine clearance > 30 ml/min (by Cockcroft-Gault formula)
• Activated partial thromboplastin time (aPTT) < 1.5 x ULN
• Prior therapy for central nervous system (CNS) disease is allowed, but at least 1 lesion > 1.5 cm is evident on MRI

Exclusion criteria

• Need for immediate local intervention for brain metastases
• Noninfectious interstitial lung disease or pneumonitis requiring glucocorticoids
• Clinically significant corneal disease
• Myocardial infarction < 6 months before, congestive heart failure (CHF), unstable angina, or serious cardiac arrhythmia