Cu64-DOTA-trastuzumab PET and Markers Predicting Response to Neoadjuvant Trastuzumab + Pertuzum in HER2+ Breast Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well copper Cu64-DOTA-trastuzumab positron emission tomography (PET) works in predicting response to treatment with trastuzumab and pertuzumab before surgery in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer that has spread from where it started to nearby tissue or lymph nodes. Diagnostic procedures, such as copper Cu 64 DOTA-trastuzumab PET, may help predict a patient's response to trastuzumab and pertuzumab before surgery in patients with locally advanced HER2 positive breast cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the standardized uptake value maximum (SUVmax) in patients with previously untreated HER2+ breast cancer. SECONDARY OBJECTIVES: I. To evaluate if the uptake of copper 64 Cu-64-DOTA-trastuzumab, a proposed indicator of responsiveness to HER2-directed therapy, correlates with serpin peptidase inhibitor alpha-1 antiproteinase, antitrypsin, member 1 gene (SERPINA1) expression, which has been shown to be associated with estrogen receptor positive (ER+)/ HER2+ patient survival, both in the HER2+/ER+ patients and in all patients. II. To compare uptake of copper Cu 64-DOTA-trastuzumab in the patients with complete pathologic response (pCR) versus (vs) non-pCR patients. OUTLINE: Patients receive trastuzumab intravenously (IV) over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV on day 0. Patients undergo PET scans at 18-24 and 42-48 hours, on day 1 and 2. Within 4 days after completion of PET scans, patients then receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks and pertuzumab IV over 30-60 minutes. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after 6 cycles of trastuzumab and pertuzumab. After completion of study treatment, patients are followed up for 1 year.

Official Title
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Use of 64Cu-DOTA-Trastuzumab PET Imaging and Molecular Markers for Prediction of Response to Trastuzumab and Pertuzum-Based Neoadjuvant Therapy

Conditions
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HER2 Positive Breast Carcinoma, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Radiation: Copper Cu 64-DOTA-Trastuzumab
* Other: Laboratory Biomarker Analysis
* Biological: Pertuzumab
* Procedure: Positron Emission Tomography
* Procedure: Therapeutic Conventional Surgery
* Biological: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be women who have histological confirmation of HER2 positive breast cancer The primary tumor must be >= 2.0cm in size and/or have biopsy proven axillary nodes that are >= 2.0cm in size by mammography, ultrasound, or magnetic resonance imaging (MRI) The current cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) Patients may not have received prior HER2 directed therapies Participants must have normal cardiac ejection fraction (per label, as defined as institutional normal) Planned neoadjuvant therapy with six cycles of combined pertuzumab, trastuzumab and chemotherapy Ability to provide informed consent Negative Serum Pregnancy test Exclusion Criteria: Participants who are not considered candidates for pertuzumab + trastuzumab + chemotherapy Concurrent malignancy other than non-melanoma skin cancer Patients must not have known metastatic disease Patients must not have received prior treatment for the current breast cancer

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (trastuzumab, copper Cu 64-DOTA-trastuzumab PET)<br>Patients receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV on day 0. Patients undergo PET scans at 18-24 and 42-48 hours, on day 1 and day 2. Within 4 days after completion of PET scans, patients receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks and pertuzumab IV over 30-60 minutes. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after 6 cycles of trastuzumab and pertuzumab. | Radiation: Copper Cu 64-DOTA-Trastuzumab<br>* Given IV<br>* Other names: 64Cu-DOTA-Trastuzumab;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: Pertuzumab<br>* Given IV<br>* Other names: RO4368451;Procedure: Positron Emission Tomography<br>* Undergo PET<br>* Other names: PET Scan;Procedure: Therapeutic Conventional Surgery<br>* Undergo surgery<br>Biological: Trastuzumab<br>* Given IV<br>* Other names: Trastuzumab Biosimilar PF-05280014;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy). | The response assessment is performed at the time of definitive surgery. Patients' disease will be staged in the conventional manner according to the AJCC. The primary endpoint is complete pathologic response defined as no evidence of residual invasive cancer in either the breast or regional lymph nodes. | Up to 1 year |