HER2 Positive Breast Carcinoma, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
Conditions
Brief summary
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
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.
Interventions
RADIATIONCopper Cu 64-DOTA-Trastuzumab
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPertuzumab
Given IV
PROCEDUREPositron Emission Tomography
Undergo PET
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
BIOLOGICALTrastuzumab
Given IV
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy). | Up to 1 year | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| SUV Measurement by 64Cu-DOTA Trastuzumab PET | Baseline | First Scan SUV Maximum, measurement by 64Cu-DOTA trastuzumab PET SUV is Standard Uptake Value. SUV = tumor activity concentration x patient body weight/injected activity decay-corrected to time of scan. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Trastuzumab, Copper Cu 64-DOTA-trastuzumab PET) 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.
Copper Cu 64-DOTA-Trastuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pertuzumab: Given IV
Positron Emission Tomography: Undergo PET
Therapeutic Conventional Surgery: Undergo surgery
Trastuzumab: Given IV | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Trastuzumab, Copper Cu 64-DOTA-trastuzumab PET) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 54.9 years |
| Race/Ethnicity, Customized Race/Ethnicity Asian; Non-Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black; Non-Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian; Hispanic or Latino | 8 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian; Non-Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Not Disclosed; Hispanic or Latino | 1 Participants |
| Region of Enrollment United States | 18 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
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.
Time frame: Up to 1 year
Population: protocol patients
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Trastuzumab, Copper Cu 64-DOTA-trastuzumab PET) | Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy). | Response | 14 Participants |
| Treatment (Trastuzumab, Copper Cu 64-DOTA-trastuzumab PET) | Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy). | Non-response | 4 Participants |
Other Pre-specified
SUV Measurement by 64Cu-DOTA Trastuzumab PET
First Scan SUV Maximum, measurement by 64Cu-DOTA trastuzumab PET SUV is Standard Uptake Value. SUV = tumor activity concentration x patient body weight/injected activity decay-corrected to time of scan.
Time frame: Baseline
Population: protocol patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Trastuzumab, Copper Cu 64-DOTA-trastuzumab PET) | SUV Measurement by 64Cu-DOTA Trastuzumab PET | 6.6 SUV |