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

Phase 4

Recruiting

• Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain
• Interventions: Other: Copper Cu 64-DOTA-Trastuzumab; Procedure: Magnetic Resonance Imaging; Device: Positron Emission Tomography; Biological: Trastuzumab; Biological: Trastuzumab Deruxtecan

• Registration Number: NCT05376878
• Lead Sponsor: City of Hope Medical Center

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.

Study Timeline

• Study First Submitted: 2022-05-03
• Study First Submitted QC: 2022-05-11
• Study First Posted: 2022-05-17
• Study Start: 2022-12-21
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-18
• Primary Completion: 2026-02-25
• Study Completion: 2026-02-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)	Magnetic Resonance Imaging	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.
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)	Trastuzumab	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.
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)	Positron Emission Tomography	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.
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)	Trastuzumab Deruxtecan	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.
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)	Copper Cu 64-DOTA-Trastuzumab	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.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States