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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-01380 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 7536 | Other Identifier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source | |
| RC1CA146456 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This clinical trial studies fluorine F 18 fluorothymidine (FLT) positron emission tomography (PET) in measuring treatment response in patients with newly diagnosed estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage I-III breast cancer. Comparing results of diagnostic procedures done before and during hormone therapy may help doctors predict a patient's response to treatment and help plan the best treatment.
PRIMARY OBJECTIVES:
I. Measure the effect of a short course of endocrine therapy on primary breast cancer metabolism and proliferation by measuring changes in serial FLT PET measures pre and post a short course of endocrine therapy.
SECONDARY OBJECTIVES:
I. Compare changes in imaging measures to tissue measures of response, in particular antigen identified by proliferation-related Ki-67 antigen (Ki-67), in the pre-therapy biopsy versus the post-therapy surgical specimen.
II. Correlate imaging measures to measures of gene expression from pre and post therapy assays to determine if there are molecular changes associated with early response to therapy.
OUTLINE:
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diagnostic (FLT PET) | Experimental | Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluorothymidine F-18 | Drug | Undergo FLT PET |
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Net Influx Constant (Ki) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. Association between Ki-67 and Ki by FLT (KFLT) decline will be analyzed using the mid-P adjustment to Fisher's exact test to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Baseline to up to 6 weeks |
| Percent Change in SUV by FLT PET | Percent change between pre-treatment (baseline) and post-therapy measurements of FLT standardized uptake value (SUV) in breast tumors will be computed. | Baseline to up to 6 weeks |
| Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample | Surgically removed breast tumor tissue is stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. | 1 to 6 weeks post-therapy start |
| Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens | Tumor tissue samples from pre-treatment (baseline) biopsy and post-treatment surgery are stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. The % values of positive cells from the baseline and post-treatment samples are then compared for each individual patient. Association between Ki-67 and KFLT decline will be analyzed to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Baseline to up to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in K1 (Blood Flow Parameter) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. | Baseline to up to 6 weeks |
| Baseline Ki (Flux Constant) Values by FLT PET |
| Measure | Description | Time Frame |
|---|---|---|
| Post-treatment Gene Expression Levels | Analyzed using BeadStudio software. Four clustering metrics for calculating dissimilarities (correlation, absolute correlation, Euclidean, and Manhattan) are available in BeadStudio and will be applied using standard analysis methods and diagnostics in BioConductor. To focus the analysis, proposed gene sets will be examined based on biological pathways and molecular signatures. |
Inclusion Criteria:
A new diagnosis of invasive breast cancer > 1.0 cm in size, ER+ clinical stage I-III
Patient must have surgical resection followed by systemic adjuvant therapy with an aromatase inhibitor (AIs) as part of planned treatment; any approved AI at standard clinical dosing may be used; in pre-menopausal patients, ovarian suppression with a gonadotropin-releasing hormone (GnRH) agonist will be started prior to initiation of the AI on a separate clinical trial in parallel with the imaging study
Have tissue block available from core biopsy for correlative biomarkers and genomic assay
Have menopausal status determined prior to study enrollment; for study purposes, postmenopausal is defined as
Negative pregnancy test within 7 days of baseline positron emission tomography (PET) scan for pre-menopausal patients
Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed
Be a candidate for [18F]FLT PET imaging
Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific screening procedures
Be willing and able to comply with scheduled visits and other trial procedures
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hannah Linden | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Diagnostic (FLT PET) | Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment. Fluorothymidine F-18: Undergo FLT PET Positron Emission Tomography: Undergo FLT PET Laboratory Biomarker Analysis: Correlative studies |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Positron Emission Tomography | Procedure | Undergo FLT PET |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Run-in (short pre-surgery course) of endocrine-targeted therapy | Drug | Patients undergo run-in (short pre-surgery course) of endocrine-targeted therapy with aromatase inhibitor between the two (baseline and repeat) FLT PET scans. This is not an experimental therapy. This is a standard of care therapy that patients will continue after surgery, when the study is completed. |
|
Ki (flux constant) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET scan
| Baseline |
| Baseline FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Baseline |
| Baseline Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Baseline |
| Post-therapy Ki (Flux Constant) Values by FLT PET | Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET | 1 to 6 weeks post-therapy start |
| Post-treatment FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the post-therapy FLT PET | 1 to 6 weeks post-therapy start |
| Post-treatment Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET | 1 to 6 weeks post-therapy start |
| 1 to 6 weeks post-therapy start |
| Pre-treatment Gene Expression Levels | Analyzed using BeadStudio software. Four clustering metrics for calculating dissimilarities (correlation, absolute correlation, Euclidean, and Manhattan) are available in BeadStudio and will be applied using standard analysis methods and diagnostics in BioConductor. To focus the analysis, proposed gene sets will be examined based on biological pathways and molecular signatures. | Baseline |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Diagnostic (FLT PET) | Patients with early stage, ER positive primary breast cancer undergo FLT PET scan at baseline and 1-6 weeks after the start of standard endocrine treatment. The surgery follows 1-7 days after the second FLT PET scan. Tracer used in the FLT PET (positron emission tomography) scanning procedure: [F18] fluorothymidine. Positron Emission Tomography: Undergo FLT PET Laboratory Biomarker Analysis: Correlative studies - Ki67 staining of the tumor tissue in the biopsy and surgical specimen. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Clinical stage | Patients presented in early clinical stages of breast cancer, with the extent of disease increasing from the stage I to IIB, as indicated in the NCI TNM staging system (v. 07/11/2014): Stage I: T1 N0; Stage IIA: T0 N1 or T1 N1 or T2 N0; Stage IIB: T2 N1 or T3 N0. Definitions: No evidence of primary tumor (T0); Primary tumor < or = 20 mm (T1); Primary tumor >20 mm but < or = 50 mm (T2); Primary tumor > 50 mm (T3); No regional lymph node metastases (N0); Metastases to movable ipsilateral level I, II axillary lymph nodes (N1). | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Net Influx Constant (Ki) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. Association between Ki-67 and Ki by FLT (KFLT) decline will be analyzed using the mid-P adjustment to Fisher's exact test to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Posted | Median | Full Range | % change | Baseline to up to 6 weeks |
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| Primary | Percent Change in SUV by FLT PET | Percent change between pre-treatment (baseline) and post-therapy measurements of FLT standardized uptake value (SUV) in breast tumors will be computed. | Posted | Median | Full Range | % change | Baseline to up to 6 weeks |
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| Primary | Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample | Surgically removed breast tumor tissue is stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. | Posted | Median | Full Range | % stained cells | 1 to 6 weeks post-therapy start |
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| Primary | Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens | Tumor tissue samples from pre-treatment (baseline) biopsy and post-treatment surgery are stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. The % values of positive cells from the baseline and post-treatment samples are then compared for each individual patient. Association between Ki-67 and KFLT decline will be analyzed to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Posted | Median | Full Range | % change | Baseline to up to 6 weeks |
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| Secondary | Percentage Change in K1 (Blood Flow Parameter) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. | Posted | Median | Full Range | % change | Baseline to up to 6 weeks |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Ki (Flux Constant) Values by FLT PET | Ki (flux constant) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET scan | Posted | Median | Full Range | mL/min/mL | Baseline |
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| Secondary | Baseline FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Posted | Median | Full Range | mL/min/mL | Baseline |
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| Secondary | Baseline Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Posted | Median | Full Range | g/mL | Baseline |
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| Secondary | Post-therapy Ki (Flux Constant) Values by FLT PET | Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET | Posted | Median | Full Range | mL/min/mL | 1 to 6 weeks post-therapy start |
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| Secondary | Post-treatment FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the post-therapy FLT PET | Posted | Median | Full Range | mL/min/mL | 1 to 6 weeks post-therapy start |
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| Secondary | Post-treatment Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET | Posted | Median | Full Range | g/mL | 1 to 6 weeks post-therapy start |
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| Other Pre-specified | Post-treatment Gene Expression Levels | Analyzed using BeadStudio software. Four clustering metrics for calculating dissimilarities (correlation, absolute correlation, Euclidean, and Manhattan) are available in BeadStudio and will be applied using standard analysis methods and diagnostics in BioConductor. To focus the analysis, proposed gene sets will be examined based on biological pathways and molecular signatures. | Not Posted | 1 to 6 weeks post-therapy start | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pre-treatment Gene Expression Levels | Analyzed using BeadStudio software. Four clustering metrics for calculating dissimilarities (correlation, absolute correlation, Euclidean, and Manhattan) are available in BeadStudio and will be applied using standard analysis methods and diagnostics in BioConductor. To focus the analysis, proposed gene sets will be examined based on biological pathways and molecular signatures. | Not Posted | Baseline | Participants |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diagnostic (FLT PET) | Patients with early stage, ER positive primary breast cancer undergo FLT PET scan at baseline and 1-6 weeks after the start of standard endocrine treatment. The surgery follows 1-7 days after the second FLT PET scan. Tracer used in the FLT PET (positron emission tomography) scanning procedure: [F18] fluorothymidine. Positron Emission Tomography: Undergo FLT PET Laboratory Biomarker Analysis: Correlative studies - Ki67 staining of the tumor tissue in the biopsy and surgical specimen. | 0 | 28 | 1 | 28 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infiltration at injection site | Injury, poisoning and procedural complications | Infiltration at injection site detected on imaging, without clinical symptoms |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hannah Linden | University of Washington / Seattle Cancer Care Alliance | 206-288-6989 | hmlinden@uw.edu |
| ID | Term |
|---|---|
| D018567 | Breast Neoplasms, Male |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C002854 | alovudine |
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Stage IIB |
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