Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer

Study Overview
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Brief Summary
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This pilot clinical trial studies how well copper Cu 64-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography (PET) works in predicting response to treatment with ado-trastuzumab emtansine in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer that has spread to other places in the body. Copper Cu 64-DOTA-trastuzumab is a chemotherapy drug (trastuzumab) attached to a radioactive substance. Diagnostic procedures using PET may allow scanners to take pictures of where the drug travels in the body and may help doctors identify which patients may benefit from treatment with ado-trastuzumab emtansine.

Detailed Description
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PRIMARY OBJECTIVES: I. Correlate uptake of 64Cu-DOTA-trastuzumab (copper Cu 64-DOTA-trastuzumab) PET by individual tumors with subsequent tumor response to ado-trastuzumab emtansine as assessed by serial 18F-fludeoxyglucose (FDG) (fludeoxyglucose F 18)/PET-computed tomography (CT). II. Compare tumor uptake of 64Cu-DOTA-trastuzumab PET between patients who do and patients who do not respond to ado-trastuzumab emtansine. III. Obtain tumor tissue for subsequent assessment of the presence of putative molecular mechanisms of resistance (MMRs) to ado-trastuzumab emtansine. When funding becomes available, those samples will be used to explore the correlation between the presence of MMRs as assessed by histopathology and tumor response to ado-trastuzumab emtansine both in univariate analysis and in combination with tumor uptake of 64Cu-DOTA-trastuzumab as measured with PET/CT. OUTLINE: Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab intravenously (IV) over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks for 1 year after initiation of treatment until disease progression. After completion of study treatment, patients are followed up for 1 year.

Official Title
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A Pilot Study of 64Cu-DOTA-Trastuzumab Positron Emission Tomography in Treatment of Advanced HER2 Positive Breast Cancer With the Antibody Drug Conjugate Ado-trastuzumab Emtansine

Conditions
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Bone Metastases, HER2-positive Breast Cancer, Liver Metastases, Lung Metastases, Recurrent Breast Cancer, Soft Tissue Metastases, Stage IV Breast Cancer

Intervention / Treatment
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* Radiation: fludeoxyglucose F 18
* Procedure: positron emission tomography
* Procedure: computed tomography
* Biological: trastuzumab
* Radiation: copper Cu 64-DOTA-trastuzumab
* Procedure: positron emission tomography
* Biological: ado-trastuzumab emtansine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained prior to initiation of chemotherapy; it should be performed within 28 days prior to enrollment (patients with a biopsy of recurrent disease that is HER2-positive and have not received HER2-directed therapy since the biopsy can exceed the 28-day window up to 6 months); patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible) At least 1 site of metastasis >= 20 mm in mean diameter must be identified The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) Patients may not have received trastuzumab within 6 weeks of projected 64Cu-DOTA-trastuzumab/PET-CT Participants must have normal cardiac ejection fraction Ability to provide informed consent Patients that may need dose reduction to commence cycle 1 treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Negative serum pregnancy test (female of childbearing potential only) Patients must have adequate cardiac function; left ventricular ejection fraction (LVEF) >= 50% as determined by multi gated acquisition (MUGA) scan or echocardiogram Exclusion Criteria: Participants who have received trastuzumab within the prior 36 days Participants who are not considered candidates for ado-trastuzumab-emtansine No metastatic sites >= 20 mm Concurrent malignancy other than skin cancer - Inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic (copper Cu 64-DOTA-trastuzumab PET)<br>Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression. | Radiation: fludeoxyglucose F 18<br>* Undergo fludeoxyglucose F 18 PET/CT<br>* Other names: FDG;Procedure: positron emission tomography<br>* Undergo fludeoxyglucose F 18 PET/CT<br>* Other names: tomography, emission computed;Procedure: computed tomography<br>* Undergo fludeoxyglucose F 18 PET/CT<br>* Other names: tomography, computed;Biological: trastuzumab<br>* Given IV<br>* Other names: MOAB HER2;Radiation: copper Cu 64-DOTA-trastuzumab<br>* Given IV<br>* Other names: 64Cu-DOTA-trastuzumab;Procedure: positron emission tomography<br>* Undergo copper Cu-DOTA-trastuzumab PET<br>* Other names: tomography, emission computed;Biological: ado-trastuzumab emtansine<br>* Given IV<br>* Other names: trastuzumab-MCC-DM1 antibody-drug conjugate;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship Between Average Tumor Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response | Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing average uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of maximum voxel standardized uptake value, SUVmax. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0). | Baseline | 
| Relationship Between Tumor Minimum Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response | Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing minimum uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of minimum voxel standardized uptake value, SUVmin. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0). | Up to 1 year |