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

Study Overview
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Brief Summary
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This clinical trial examines an investigational scan (64Cu-DOTA-trastuzumab positron emission tomography [PET]/magnetic resonance imaging [MRI]) in imaging patients with HER2+ breast cancer that has spread to the brain (brain metastasis). Diagnostic procedures, such as 64Cu-DOTA-trastuzumab PET/MRI, may help find HER2+ breast cancer that has spread to the brain and determine whether cancer in the brain takes up trastuzumab, which may predict for response to trastuzumab deruxtecan (the standard of care chemotherapy).

Detailed Description
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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.

Official Title
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Pilot Study to Evaluate 64Cu-DOTA-Trastuzumab Imaging in Patients With HER2+ Breast Cancer With Brain Metastatsis Treated With Fam-Trastuzumab Deruxtecan

Conditions
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Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain

Intervention / Treatment
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* Other: Copper Cu 64-DOTA-Trastuzumab
* Procedure: Magnetic Resonance Imaging
* Device: Positron Emission Tomography
* Biological: Trastuzumab
* Biological: Trastuzumab Deruxtecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)<br>Patients receive trastuzumab 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. | Other: Copper Cu 64-DOTA-Trastuzumab<br>* Given IV<br>* Other names: 64Cu-DOTA-Trastuzumab;Procedure: Magnetic Resonance Imaging<br>* Undergo PET/MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Device: Positron Emission Tomography<br>* Undergo PET/MRI<br>* Other names: proton magnetic resonance spectroscopic imaging;Biological: Trastuzumab<br>* Given IV<br>* Other names: Trazimera;Biological: Trastuzumab Deruxtecan<br>* Given IV<br>* Other names: WHO 10516;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with quantifiable 64Cu-DOTA-trastuzumab PET uptake | Percentage of patient with quantifiable 64Cu-DOTA-trastuzumab PET imaging (maximum standardized uptake value[SUVmax]) uptake in brain lesions. | Until disease progression or death, up to 5 years. | 
| Comparison of average min SUVmax values in responders versus non-responders. | Comparison evaluated using a non-parametric test. The lowest SUVmax (minimum SUVmax) across the lesions will be the primary metric used. Response assessment for CNS disease is determined by MRI of the brain using Response Assessment in Neuro-Oncology (RANO) criteria. | Until disease progression or death, up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. | From start of treatment until progression or death from any cause, up to 5 years. |