Positron Emission Tomography in Women With Advanced HER2-Positive Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Diagnostic procedures, such as copper Cu 64-DOTA-trastuzumab-labeled PET, may help doctors to plan a better treatment PURPOSE: This pilot trial is studying copper Cu 64-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab-labeled positron emission tomography (PET) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Determine the dose of pre-administered cold antibody that optimizes image quality of 64Cu-DOTA-trastuzumab PET without increasing the radiation dose to the heart in women with metastatic HER2 positive breast cancer. II. Determine whether tumor uptake on 64Cu-DOTA-trastuzumab PET correlates with tumor expression of HER2 in women with metastatic disease. III. Perform an exploratory analysis of the relationship between uptake on 64Cu-DOTA-trastuzumab PET, HER2 overexpression, and inactivation of the PI3K/Akt pathway. OUTLINE: This is a part one dose-determining study followed by a part two study. PART ONE: Patients are randomized to 1 of 3 dose levels. Patients undergo a PET scan 24-48 hours after injection of 64 Cu-DOTA-trastuzumab. PART TWO: Patients undergo a PET scan 24-48 hours after injection of 64 Cu-DOTA-trastuzumab at the optimal dose as determined in part one of the study.

Official Title
-----------------
64 Cu-DOTA-Trastuzumab Positron Emission Tomography in Women With Advanced HER2 Positive Invasive Breast Cancer

Conditions
-----------------
Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
-----------------
* Procedure: positron emission tomography
* Radiation: copper Cu 64-DOTA-trastuzumab
* Procedure: Biopsy
* Other: Immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Genetic: mutation analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Eligibility Part I (Determination of the cold dose) 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 within 28 days prior to study. 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 non-hepatic site of metastasis greater than or equal to 2 cm in mean diameter must be identified in addition to the site that was biopsied. The cancer must over express HER2 as determined by IHC and FISH. Patients may have received trastuzumab in the adjuvant, neoadjuvant, or metastatic setting, but cannot have received the drug within the prior 2 months. Participants must have normal cardiac ejection fraction. Eligibility Part 2 (correlation of HER2 expression with PET uptake) 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 within 28 days prior to study. 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 non-hepatic site of metastasis site greater than or equal to 2 cm in mean diameter must be identified in addition to the site that was biopsied. Participants with HER2 1+, 2+ and 3+ by IHC are eligible. Patients may have received trastuzumab in the adjuvant, neoadjuvant, or metastatic setting, but cannot have received the drug within the prior 2 months. Participants must have normal cardiac ejection fraction. Ineligibility Participants who have received trastuzumab within the prior 2 months Participants who are not considered candidates for trastuzumab Metastatic disease in a single site No metastatic site greater than or equal to 2 cm Concurrent malignancy other than skin cancer Inability to provide informed consent Participants who are pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>PART ONE: Patients are randomized to 1 of 3 dose levels. Patients undergo a PET scan 24-48 hours after injection of copper Cu 64-DOTA-trastuzumab. PART TWO: Patients undergo a PET scan 24-48 hours after injection of copper Cu 64-DOTA-trastuzumab. | Procedure: positron emission tomography<br>* PET images performed on a GE Discovery 16 Ste PET-CT scanner<br>* Other names: tomography, emission computed;Radiation: copper Cu 64-DOTA-trastuzumab<br>* 15 mCi of Cu 64-DOTA-trastuzumab, total trastuzumab dose less than 5 mg.<br>* Other names: 64Cu-DOTA-trastuzumab;Procedure: Biopsy<br>* Correlative Studies<br>* Other names: biopsies;Other: Immunohistochemistry staining method<br>* Correlative studies<br>* Other names: immunohistochemistry;Other: laboratory biomarker analysis<br>* Correlative studies<br>Genetic: mutation analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Uptake of 64Cu-DOTA-trastuzumab After 24 Hours | Comparison of uptake between the HER2+ and HER2- groups, treating SUVmax measurements for individual tumors as independent observations. Statistical significance of differences in SUVmax between patient groups was assessed via a nonparametric (Wilcoxon rank-sum) test. Radiolabel uptake for tumors was measured in terms of single-voxel maximum SUV (SUVmax; SUV = tissue activity per mL x body weight [g]/injected activity decay-corrected to time of scan). | 24 hours after injection of 64 CU-DOTA-trastuzumab | 
| Tumor Uptake of 64Cu-DOTA-trastuzumab After 48 Hours | Comparison of uptake between the HER2+ and HER2- groups, treating SUVmax measurements for individual tumors as independent observations. Statistical significance of differences in SUVmax between patient groups was assessed via a nonparametric (Wilcoxon rank-sum) test. Radiolabel uptake for tumors was measured in terms of single-voxel maximum SUV (SUVmax; SUV = tissue activity per mL x body weight [g]/injected activity decay-corrected to time of scan). | 48 hours after injection of 64 CU-DOTA-trastuzumab | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2-positive breast cancer