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FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

Primary Purpose

Estrogen Receptor Positive, HER2/Neu Negative, Male Breast Carcinoma

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fluorothymidine F-18
Positron Emission Tomography
Laboratory Biomarker Analysis
Run-in (short pre-surgery course) of endocrine-targeted therapy
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Estrogen Receptor Positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (FLT PET)

Arm Description

Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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 Ki (Flux Constant) Values by FLT PET
Ki (flux constant) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET scan
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 Standardized Uptake Values (SUV) by FLT PET
FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET
Post-therapy Ki (Flux Constant) Values by FLT PET
Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET
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
Post-treatment Standardized Uptake Values (SUV) by FLT PET
FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET

Full Information

First Posted
August 20, 2013
Last Updated
April 13, 2018
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01928186
Brief Title
FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer
Official Title
Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
July 20, 2015 (Actual)
Study Completion Date
July 20, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Estrogen Receptor Positive, HER2/Neu Negative, Male Breast Carcinoma, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (FLT PET)
Arm Type
Experimental
Arm Description
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
Intervention Type
Drug
Intervention Name(s)
Fluorothymidine F-18
Other Intervention Name(s)
18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine
Intervention Description
Undergo FLT PET
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan
Intervention Description
Undergo FLT PET
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Run-in (short pre-surgery course) of endocrine-targeted therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Change in Net Influx Constant (Ki) by FLT PET
Description
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.
Time Frame
Baseline to up to 6 weeks
Title
Percent Change in SUV by FLT PET
Description
Percent change between pre-treatment (baseline) and post-therapy measurements of FLT standardized uptake value (SUV) in breast tumors will be computed.
Time Frame
Baseline to up to 6 weeks
Title
Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample
Description
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.
Time Frame
1 to 6 weeks post-therapy start
Title
Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens
Description
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.
Time Frame
Baseline to up to 6 weeks
Secondary Outcome Measure Information:
Title
Percentage Change in K1 (Blood Flow Parameter) by FLT PET
Description
Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed.
Time Frame
Baseline to up to 6 weeks
Title
Baseline Ki (Flux Constant) Values by FLT PET
Description
Ki (flux constant) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET scan
Time Frame
Baseline
Title
Baseline FLT Transport (K1) Values by FLT PET
Description
K1 (blood flow measure) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET
Time Frame
Baseline
Title
Baseline Standardized Uptake Values (SUV) by FLT PET
Description
FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET
Time Frame
Baseline
Title
Post-therapy Ki (Flux Constant) Values by FLT PET
Description
Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET
Time Frame
1 to 6 weeks post-therapy start
Title
Post-treatment FLT Transport (K1) Values by FLT PET
Description
K1 (blood flow measure) in breast tumor tissue as determined by the post-therapy FLT PET
Time Frame
1 to 6 weeks post-therapy start
Title
Post-treatment Standardized Uptake Values (SUV) by FLT PET
Description
FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET
Time Frame
1 to 6 weeks post-therapy start
Other Pre-specified Outcome Measures:
Title
Post-treatment Gene Expression Levels
Description
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.
Time Frame
1 to 6 weeks post-therapy start
Title
Pre-treatment Gene Expression Levels
Description
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.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannah Linden
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

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