Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain
Conditions
Brief summary
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
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.
Interventions
Given IV
PROCEDUREMagnetic Resonance Imaging
Undergo PET/MRI
DEVICEPositron Emission Tomography
Undergo PET/MRI
BIOLOGICALTrastuzumab
Given IV
BIOLOGICALTrastuzumab Deruxtecan
Given IV
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of average min SUVmax values in responders versus non-responders. | Until disease progression or death, up to 5 years. | 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. |
| Percent of patients with quantifiable 64Cu-DOTA-trastuzumab PET uptake | Until disease progression or death, up to 5 years. | Percentage of patient with quantifiable 64Cu-DOTA-trastuzumab PET imaging (maximum standardized uptake value\[SUVmax\]) uptake in brain lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From start of treatment until progression or death from any cause, up to 5 years. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoanne E Mortimer
City of Hope Medical Center
Outcome results
None listed