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

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.

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