Monitoring Early Response to Targeted Therapy in Stage IV HER2+ Breast Cancer Patients With Advanced PET/MR Imaging

Study Overview
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Brief Summary
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The purpose of the study is to see if a new group of imaging tests can help identify response to stage IV HER2+ breast cancer before treatment.

Detailed Description
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The purpose of this study is to see if a new group of imaging tests can help identify response to stage IV human epidermal growth factor receptor 2 positive (HER2+) breast cancer before and during treatment. This study will test a new method for monitoring treatment. The investigators will use [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) to look at previously diagnosed stage IV breast cancer and image up to three times during therapy. FDG is a non-natural amino acid with a radioactive tag that is used clinically for staging of disease. However, the role of FDG-PET/MRI for imaging response in breast cancer is not currently clear. PET/MRI is a new imaging technique that combines PET and MRI into a single study.

Official Title
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Monitoring Early Response to Targeted Therapy in Stage IV Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer Patients With Advanced Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: [18F]-FDG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥ 18 years old and ≤ 75 years old Patients with HER2+ metastatic breast cancer HER2-positive breast cancer prospectively determined on the primary tumor by a local pathology laboratory and defined as immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) (defined by ISH ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies). Only one positive result is required for eligibility Estrogen/progesterone receptor positive OR negative disease allowed Patients must have measurable disease in one metastatic lesion per RECIST v 1.1 Stage IV HER2+ breast cancer patients eligible for a new therapeutic regimen that includes HER2-targeted treatment who are naïve to that regimen Estimated life expectancy of greater than six months Exclusion Criteria: Children, less than 18 years of age, will be excluded from this study Metastatic breast cancer patients who are HER2 positive and have already started their current HER2-targeted therapy regimen for metastatic disease Patients who have not recovered from grade 2 or higher toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment Patient is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 7 months after the last dose of study treatment Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection that requires systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent). Patients found to have constitutionally present non-magnetic resonance (MR) compatible ferromagnetic materials Unable to lie still on the imaging table for one (1) hour Inability to receive gadolinium-based contrast agent Patients for whom a PET/MRI is technically not feasible (e.g. breast volume, obesity, > body mass index (BMI) 36)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: [18F]-Fluorodeoxyglucose (FDG) PET/ MRI<br> | Drug: [18F]-FDG<br>* [18F]-FDG will be injected prior to PET/MRI imaging up to three times over the course of six months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline measure of PET standardized uptake value (SUV). | Compare baseline metrics from PET/MRI | Baseline imaging visit 1 | 
| Baseline measure of apparent diffusion coefficient (ADC) in mm2/sec from MRI. | Compare baseline metrics from PET/MRI | Baseline imaging visit 1 | 
| Baseline measure of signal enhancement ratio (SER) from MRI. | Compare baseline metrics from PET/MRI | Baseline imaging visit 1 | 
| Changes in SER from MRI | Compare percent change of SER from imaging visit 3 to the baseline. | Baseline through 6 months | 
| Changes in ADC from MRI | Compare percent change of ADC (mm2/sec) from imaging visit 3 to the baseline. | Baseline through 6 months | 
| Changes in SUV from PET | Compare percent change of SUV from imaging visit 3 to the baseline. | Baseline through 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Follow-up | Compare changes in imaging metrics to disease progression (defined as clinical progression of disease through increase in lesion size or increase in number of lesions). | Baseline through 5 year follow-up | 
| Changes in ADC (mm2/sec) from MRI. | Compare percent change from imaging visit 2 to the baseline. | Baseline through 2 months | 
| Changes in SER from MRI. | Compare percent change from imaging visit 2 to the baseline. | Baseline through 2 months | 
| Changes in SUV from PET. | Compare percent change from imaging visit 2 to the baseline. | Baseline through 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FDG-PET, MRI, quantitative imaging