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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

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ClinicalTrials.gov Identifier: NCT01928186
Recruitment Status : Completed
First Posted : August 23, 2013
Results First Posted : September 25, 2017
Last Update Posted : May 15, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Hannah Linden, University of Washington

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.

Condition or disease Intervention/treatment Phase
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 Drug: Fluorothymidine F-18 Procedure: Positron Emission Tomography Other: Laboratory Biomarker Analysis Drug: Run-in (short pre-surgery course) of endocrine-targeted therapy Not Applicable

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 : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET
Study Start Date : September 2011
Actual Primary Completion Date : July 20, 2015
Actual Study Completion Date : July 20, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Diagnostic (FLT PET)
Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
Drug: Fluorothymidine F-18
Undergo FLT PET
Other Names:
  • 18F-FLT
  • 3'-deoxy-3'-[18F]fluorothymidine

Procedure: Positron Emission Tomography
Undergo FLT PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Run-in (short pre-surgery course) of endocrine-targeted therapy
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 Measures :
  1. 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.


  2. 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.

  3. 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.

  4. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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


Other Outcome Measures:
  1. 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.

  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01928186


Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Hannah Linden Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Responsible Party: Hannah Linden, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier: NCT01928186     History of Changes
Other Study ID Numbers: 7536
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 )
RC1CA146456 ( U.S. NIH Grant/Contract )
First Posted: August 23, 2013    Key Record Dates
Results First Posted: September 25, 2017
Last Update Posted: May 15, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs