Breast Cancer, Stage IV Breast Cancer
Conditions
Keywords
HER2-positive breast cancer
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.
Interventions
GENETICmutation analysis
Correlative studies
RADIATIONcopper Cu 64-DOTA-trastuzumab
15 mCi of Cu 64-DOTA-trastuzumab, total trastuzumab dose less than 5 mg.
PROCEDUREBiopsy
Correlative Studies
OTHERImmunohistochemistry staining method
Correlative studies
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREpositron emission tomography
PET images performed on a GE Discovery 16 Ste PET-CT scanner
Sponsors
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Uptake of 64Cu-DOTA-trastuzumab After 24 Hours | 24 hours after injection of 64 CU-DOTA-trastuzumab | 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). |
| Tumor Uptake of 64Cu-DOTA-trastuzumab After 48 Hours | 48 hours after injection of 64 CU-DOTA-trastuzumab | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HER2+ Patients HER2+ patients underwent 64Cu-DOTA-trastuzumab injection, preceded by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) hours after 64Cu-DOTA-trastuzumab injection. Radio-label uptake in prominent lesions was measured as SUVmax. | 11 |
| HER2- Patients HER2- patients underwent 64Cu-DOTA-trastuzumab injection, preceded by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) hours after 64Cu-DOTA-trastuzumab injection. Radio-label uptake in prominent lesions was measured as SUVmax. | 7 |
| Total | 18 |
Baseline characteristics
| Characteristic | HER2+ Patients | HER2- Patients | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 61 years | 60 years |
| Race/Ethnicity, Customized African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 11 participants | 7 participants | 18 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 7 |
| other Total, other adverse events | 0 / 11 | 0 / 7 |
| serious Total, serious adverse events | 0 / 11 | 0 / 7 |
Outcome results
Primary
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).
Time frame: 24 hours after injection of 64 CU-DOTA-trastuzumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HER2+ Patients | Tumor Uptake of 64Cu-DOTA-trastuzumab After 24 Hours | 7.0 SUVmax (g/mL) |
| HER2- Patients | Tumor Uptake of 64Cu-DOTA-trastuzumab After 24 Hours | 3.7 SUVmax (g/mL) |
p-value: <0.001Wilcoxon rank-sum
Primary
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).
Time frame: 48 hours after injection of 64 CU-DOTA-trastuzumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HER2+ Patients | Tumor Uptake of 64Cu-DOTA-trastuzumab After 48 Hours | 8.7 SUVmax (g/mL) |
| HER2- Patients | Tumor Uptake of 64Cu-DOTA-trastuzumab After 48 Hours | 4.6 SUVmax (g/mL) |
p-value: <0.001Wilcoxon rank-sum