Male Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer
Conditions
Brief summary
This clinical trial studies fludeoxyglucose F 18 (FDG) positron emission tomography (PET) and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) in predicting response to treatment in patients with breast cancer. Comparing results of diagnostic procedures done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether detailed kinetic analysis of FDG PET and magnetic resonance (MR) imaging studies for measures of tumor metabolism and blood perfusion can predict response and outcome for breast cancer patients undergoing neo-adjuvant therapy. II. To compare the in vivo tumor biology associated with responsive and resistant tumors as measured by kinetic changes in FDG PET and MR imaging parameters to tumor subtypes analyzed from assay of pre-therapy biopsy and post-therapy surgical tissue. OUTLINE: Patients undergo FDG PET and DCE-MRI 1-2 weeks before prior to chemotherapy initiation, between 1-12 weeks after initiation of the first course of chemotherapy, and after the completion of chemotherapy (within 4 weeks prior to surgery).
Interventions
RADIATIONfludeoxyglucose F 18
Undergo FDG PET
DEVICEpositron emission tomography
Undergo FDG PET
DEVICEdynamic contrast-enhanced magnetic resonance imaging
Undergo DCE-MRI
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy * Primary tumor 2.0 cm or greater, and/or clinical evidence of axillary disease (palpable N1 or N2 or biopsy proven) * No obvious contraindications for primary chemotherapy * Able to lie still for PET and MRI scanning * Able to understand and willing to sign a written informed consent document and a Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines
Exclusion criteria
* Serious systemic illness other than breast cancer * Contraindication to MRI or history of adverse reaction to gadolinium * Evidence of distant disease outside of regional lymph nodes * Pregnant * Poorly controlled diabetes mellitus (fasting blood glucose \> 200) * Prior systemic cancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Favorable Pathologic Response at Surgery | At time of surgery | The primary clinical endpoint is dichotomous (yes/no) - Has patient achieved favorable microscopic pathologic response at surgery? This favorable pathologic response is defined as: 1. No evidence of microscopic invasive tumor at the primary tumor site and in regional axillary lymph nodes = Residual Cancer Burden class 0 (RCB 0) 2. Minimal invasive residual disease at primary tumor site and/or in regional axillary lymph nodes = Residual Cancer Burden class I (RCB I) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in PET K1 Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | Baseline to up to 12 weeks (mid-therapy) | Percent change in tumor perfusion between pre-therapy and mid-therapy FDG PET scans as represented by the PET measure K1 (parametric) % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response. |
| Percent Change in Tumor Metabolism / Perfusion Ratio (MRFDG/K1) Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | Baseline to up to 12 weeks (mid-therapy) | Percent change in tumor metabolism / perfusion ratio between pre-therapy and mid-therapy FDG PET scans as represented by the PET measure MRFDG/K1 (parametric) % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response. |
| Time From Surgery to Breast Cancer Recurrence | The time from surgery to breast cancer recurrence. If recurrence does not occur during follow-up, the endpoint will be censored at the time of last documented disease-free status. | Mean (range) |
| Time of Surgery to Overall Survival | Overall survival from time of surgery. If death does not occur during follow-up, the endpoint will be censored at the date of last contact when the patient was verified as alive. | Mean (range) |
| Percent Change in DCE-MRI Peak Percent Enhancement (Peak PE) Between Mid-therapy and Pre-therapy Breast MRI Scans and Its Association With Pathologic Response | Baseline to up to 12 weeks (mid-therapy) | Percent change in tumor enhancement between pre-therapy and mid-therapy DCE-MRI scans as represented by the MRI measure Peak PE % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnostic (FDG PET and DCE-MRI) Patients undergo FDG PET and DCE-MRI 1-2 weeks prior to chemotherapy initiation, between 1-12 weeks after initiation of the first course of chemotherapy, and after the completion of chemotherapy (within 4 weeks prior to surgery).
fludeoxyglucose F 18: Undergo FDG PET
positron emission tomography: Undergo FDG PET
dynamic contrast-enhanced magnetic resonance imaging: Undergo DCE-MRI
laboratory biomarker analysis: Correlative studies | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Diagnostic (FDG PET and DCE-MRI) |
|---|---|
| Age, Continuous | 43 years |
| Clinical stage IIA | 9 Participants |
| Clinical stage IIB | 8 Participants |
| Clinical stage IIIA | 9 Participants |
| Clinical stage IIIB | 3 Participants |
| Clinical stage IIIC | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
Number of Participants With Favorable Pathologic Response at Surgery
The primary clinical endpoint is dichotomous (yes/no) - Has patient achieved favorable microscopic pathologic response at surgery? This favorable pathologic response is defined as: 1. No evidence of microscopic invasive tumor at the primary tumor site and in regional axillary lymph nodes = Residual Cancer Burden class 0 (RCB 0) 2. Minimal invasive residual disease at primary tumor site and/or in regional axillary lymph nodes = Residual Cancer Burden class I (RCB I)
Time frame: At time of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Number of Participants With Favorable Pathologic Response at Surgery | 11 Participants |
Secondary
Percent Change in DCE-MRI Peak Percent Enhancement (Peak PE) Between Mid-therapy and Pre-therapy Breast MRI Scans and Its Association With Pathologic Response
Percent change in tumor enhancement between pre-therapy and mid-therapy DCE-MRI scans as represented by the MRI measure Peak PE % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response.
Time frame: Baseline to up to 12 weeks (mid-therapy)
Population: One participant had to be excluded from this analysis:~\[1\] pathologic response could not be evaluated due to a metastatic disease progression prior to surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Percent Change in DCE-MRI Peak Percent Enhancement (Peak PE) Between Mid-therapy and Pre-therapy Breast MRI Scans and Its Association With Pathologic Response | -31 percent change |
| Patients Without Favorable Pathologic Response | Percent Change in DCE-MRI Peak Percent Enhancement (Peak PE) Between Mid-therapy and Pre-therapy Breast MRI Scans and Its Association With Pathologic Response | -14 percent change |
Secondary
Percent Change in PET K1 Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response
Percent change in tumor perfusion between pre-therapy and mid-therapy FDG PET scans as represented by the PET measure K1 (parametric) % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response.
Time frame: Baseline to up to 12 weeks (mid-therapy)
Population: Three participants had to be excluded from this analysis:~1. mid-therapy PET images got lost due to a technical error;~2. pre-therapy scanning procedure had 40 seconds delayed start, preventing the modeling of parametric outcomes;~3. pathologic response could not be evaluated due to a metastatic disease progression prior to surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Percent Change in PET K1 Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | -71.2 percent change |
| Patients Without Favorable Pathologic Response | Percent Change in PET K1 Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | -55.8 percent change |
Secondary
Percent Change in Tumor Metabolism / Perfusion Ratio (MRFDG/K1) Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response
Percent change in tumor metabolism / perfusion ratio between pre-therapy and mid-therapy FDG PET scans as represented by the PET measure MRFDG/K1 (parametric) % change: (Mid-Pre)/Pre, compared between groups of patients who did or did not achieve favorable pathologic response.
Time frame: Baseline to up to 12 weeks (mid-therapy)
Population: Three participants had to be excluded from this analysis:~1. mid-therapy PET images got lost due to a technical error;~2. pre-therapy scanning procedure had 40 seconds delayed start, preventing the modeling of parametric outcomes;~3. pathologic response could not be evaluated due to a metastatic disease progression prior to surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Percent Change in Tumor Metabolism / Perfusion Ratio (MRFDG/K1) Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | -45.0 percent change |
| Patients Without Favorable Pathologic Response | Percent Change in Tumor Metabolism / Perfusion Ratio (MRFDG/K1) Between Mid-therapy and Pre-therapy FDG PET Scans and Its Association With Pathologic Response | -68.5 percent change |
Secondary
Time From Surgery to Breast Cancer Recurrence
Mean (range)
Time frame: The time from surgery to breast cancer recurrence. If recurrence does not occur during follow-up, the endpoint will be censored at the time of last documented disease-free status.
Population: At the time of final analysis, 7 of the 35 patients (20%) had recurrence.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Time From Surgery to Breast Cancer Recurrence | 2.9 years- recurrence free |
Secondary
Time of Surgery to Overall Survival
Mean (range)
Time frame: Overall survival from time of surgery. If death does not occur during follow-up, the endpoint will be censored at the date of last contact when the patient was verified as alive.
Population: At the time of final analysis, 4 of the 35 patients (11%) had died.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diagnostic (FDG PET and DCE-MRI) | Time of Surgery to Overall Survival | 3.1 years- overall survival |