- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01928186
FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer
Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- A prior documented bilateral oophorectomy, or
- A history of at least 12 months without spontaneous menstrual bleeding, or
- Age 60 or older with a prior hysterectomy without oophorectomy, or
- Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown) with a documented follicle-stimulating hormone (FSH) level demonstrating confirmatory elevation in the postmenopausal range for the lab
- 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:
- Current use of aromatase inhibitor as prevention or treatment for breast cancer
- Life expectancy of less than two months
- HER2/neu positive by IHC and/or another FDA approved HER2 testing method
- Inability to tolerate scanning (e.g. - claustrophobia, severe pain)
- Weight exceeding capacity of imaging table
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
|
Correlative studies
Undergo FLT PET
Other Names:
Undergo FLT PET
Other Names:
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change in Net Influx Constant (Ki) by FLT PET
Time Frame: Baseline to up to 6 weeks
|
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
Time Frame: Baseline to up to 6 weeks
|
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
Time Frame: 1 to 6 weeks post-therapy start
|
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
Time Frame: Baseline to up to 6 weeks
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage Change in K1 (Blood Flow Parameter) by FLT PET
Time Frame: Baseline to up to 6 weeks
|
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
Time Frame: Baseline
|
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
Time Frame: Baseline
|
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
Time Frame: Baseline
|
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
Time Frame: 1 to 6 weeks post-therapy start
|
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
Time Frame: 1 to 6 weeks post-therapy start
|
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
Time Frame: 1 to 6 weeks post-therapy start
|
FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET
|
1 to 6 weeks post-therapy start
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Post-treatment Gene Expression Levels
Time Frame: 1 to 6 weeks post-therapy start
|
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.
|
1 to 6 weeks post-therapy start
|
Pre-treatment Gene Expression Levels
Time Frame: Baseline
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 7536 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2013-01380 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RC1CA146456 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stage IIIA Breast Cancer
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)Active, not recruitingStage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Case Comprehensive Cancer CenterNational Institute on Minority Health and Health Disparities (NIMHD)CompletedCancer Survivor | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Ohio State University Comprehensive Cancer CenterCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of ArizonaNational Cancer Institute (NCI)CompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast CancerUnited States
-
Robert H. Lurie Cancer CenterNational Cancer Institute (NCI)WithdrawnStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of Colorado, DenverActive, not recruitingStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Healthy SubjectUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States