Estrogen Receptor Positive, Recurrent Breast Carcinoma, Stage IV Breast Cancer AJCC v6 and v7
Conditions
Brief summary
This clinical trial studies use of F-18 16 alpha-fluoroestradiol (\[F-18\] FES) positron emission tomography (PET)/computed tomography (CT) in measuring tumor hormone receptor expression in patients undergoing endocrine-targeted therapy for newly diagnosed breast cancer or breast cancer that has come back or spread to other places in the body. Comparing results of diagnostic procedures done before, during, and after hormone therapy may help measure a patient's response to treatment.
Detailed description
PRIMARY OBJECTIVES: I. Measure the effect of endocrine targeted therapy on estrogen receptor (ER) expression and estradiol binding to the receptor using serial FES PET and fludeoxyglucose F-18 (FDG) PET. SECONDARY OBJECTIVES: I. Document the safety profile of FES PET in patients with breast cancer. II. Examine associations between FES PET results and serial measurements of hormone or other levels in peripheral blood, as related to efficacy of endocrine-targeted therapy. Correlate FES PET uptake measures with histopathological assays and tumor microenvironment studies on biopsy specimens, if relevant to specific treatment regimen. OUTLINE: Patients undergo F-18 FES PET/CT scan at baseline. Patients also undergo F-18 FES PET/CT and FDG PET/CT between 1-12 weeks after starting therapy, and then 1-12 weeks after the second FES PET/CT scan. Repeat FDG PET may be omitted in patients on selective estrogen receptor degrader. After completion of study, patients are followed up for up to 20 years.
Interventions
PROCEDUREComputed Tomography
Undergo F-18 FES PET/CT
Undergo F-18 FES PET/CT
DRUGFludeoxyglucose F-18
Undergo FDG PET/CT
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREPositron Emission Tomography
Undergo F-18 FES PET/CT
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
* Adult, non-pregnant patients with biopsy-proven or clinically obvious primary, recurrent or metastatic breast cancer * Breast cancer from ER+ primary that is seen on other imaging tests; tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease * At least one site of disease 1.5 cm or greater is needed to meet the spatial resolution limits of PET imaging * Patients must have been off tamoxifen or other estrogen receptor blocking agents for at least 6 weeks and off chemotherapy for 3 weeks for the initial baseline FES * Patients must be selected for an endocrine targeted therapy regimen for treatment of their breast cancer by the referring oncologist; selected treatments may be part of experimental treatment protocols for which the patient would be separately consented * Patients must be willing to undergo serial imaging procedures * Patients must agree to allow access to clinical records regarding response to treatment and long term follow up
Exclusion criteria
* An inability to lie still for the tests * Individuals weighing more than 300 lb; (this is the weight limit of the scanner table) * Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded * Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication) * Use of tamoxifen, Faslodex, diethylstilbestrol (DES) or any other ER blocking agent \< 6 weeks or chemotherapy \< 3 weeks prior to imaging scan * Unwillingness or inability to give informed consent * Uncontrolled diabetes mellitus (fasting glucose \> 200 mg/dL) * Adult patients who require monitored anesthesia for PET scanning
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | Uptake was quantified using lean body mass adjusted SUV (SULmean). The geometric mean was calculated for up to 3 lesions per patient. Systematic change in FES SULgmean between baseline and a second FES scan at approximately 2 or 8 weeks and a third FES scan was at approximately 8 weeks measured using a sign test where the median change is zero. |
| F-18 16 Alpha-fluoroestradiol (FES) Uptake | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | Quantitative and qualitative measures of FES uptake for each disease site, a set of 1.5 cm diameter regions on three adjacent planes with the highest lesion FES uptake will be drawn to determine maximal FES uptake. Up to 10 sites seen on the static torso survey will be quantified. Lesions will qualitatively determined to be visible or not visible. |
| Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | The number of patients showing a 20% increase in FES SULgmean compared to baseline at either 2 or 8 weeks using a 90% Wilson score binomial confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression | from start of therapy up to 20 years | Months from the start of endocrine therapy to the time the patient is first recorded as having disease progression, |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnostic (F-18 FES PET/CT) Patients undergo F-18 FES PET/CT scan at baseline. Patients also undergo F-18 FES PET/CT and FDG PET/CT between 1-12 weeks after starting therapy, and then 1-12 weeks after the second FES PET/CT scan. Repeat FDG PET may be omitted in patients on selective estrogen receptor degrader. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Diagnostic (F-18 FES PET/CT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 25 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 29 |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV
Uptake was quantified using lean body mass adjusted SUV (SULmean). The geometric mean was calculated for up to 3 lesions per patient. Systematic change in FES SULgmean between baseline and a second FES scan at approximately 2 or 8 weeks and a third FES scan was at approximately 8 weeks measured using a sign test where the median change is zero.
Time frame: from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)
Population: 15/23 patients underwent a second FES PET/CT scan approximately 2 wks after starting potential ER modulating (vorinostat) therapy. 14/23 underwent a second or third FES PET/CT scan approximately 8 wks after starting vorinostat therapy. 6 patients underwent a second FES PET/CT scan between 2-8 wks after starting potential ER blocking therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FES-imaging After 2 Wks of ER Modulating (Vorinostat) Therapy | Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV | 8.7 percentage of change in SULgmean |
| FES-imaging After 8 Wks of ER Modulating (Vorinostat) Therapy | Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV | 1.9 percentage of change in SULgmean |
| FES-imaging After 2-8 Weeks of ER Blocking Therapy | Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV | -60.3 percentage of change in SULgmean |
Primary
F-18 16 Alpha-fluoroestradiol (FES) Uptake
Quantitative and qualitative measures of FES uptake for each disease site, a set of 1.5 cm diameter regions on three adjacent planes with the highest lesion FES uptake will be drawn to determine maximal FES uptake. Up to 10 sites seen on the static torso survey will be quantified. Lesions will qualitatively determined to be visible or not visible.
Time frame: from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)
Population: quantitative and qualitative measure of FES positive lesions
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| FES-imaging After 2 Wks of ER Modulating (Vorinostat) Therapy | F-18 16 Alpha-fluoroestradiol (FES) Uptake | 281 number of ER+ lesions |
| FES-imaging After 8 Wks of ER Modulating (Vorinostat) Therapy | F-18 16 Alpha-fluoroestradiol (FES) Uptake | 243 number of ER+ lesions |
Primary
Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV)
The number of patients showing a 20% increase in FES SULgmean compared to baseline at either 2 or 8 weeks using a 90% Wilson score binomial confidence interval.
Time frame: from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)
Population: The patient arms different from Primary Outcome 1 because they are separated according to the type of therapy each group had (ER modulating or ER blocking), not by the number of FES scans that they had. Results are based on the change between 2 scans.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FES-imaging After 2 Wks of ER Modulating (Vorinostat) Therapy | Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) | 0 Proportion of participants |
| FES-imaging After 8 Wks of ER Modulating (Vorinostat) Therapy | Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) | 0 Proportion of participants |
Secondary
Time to Disease Progression
Months from the start of endocrine therapy to the time the patient is first recorded as having disease progression,
Time frame: from start of therapy up to 20 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FES-imaging After 2 Wks of ER Modulating (Vorinostat) Therapy | Time to Disease Progression | 2 months |
| FES-imaging After 8 Wks of ER Modulating (Vorinostat) Therapy | Time to Disease Progression | 5.6 months |