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

Stage IIIA Breast Cancer Clinical Trial

Official title:

Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01928186
• Other study ID #: 7536
• Secondary ID: NCI-2013-0138075
• Status: Completed
• Phase: N/A
• Start date: September 2011
• Est. completion date: July 20, 2015

Study information

• Verified date: April 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 20, 2015
• Est. primary completion date: July 20, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• 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

Intervention

Drug:
• Fluorothymidine F-18
Undergo FLT PET

Procedure:
• Positron Emission Tomography
Undergo FLT PET

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.

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	1 to 6 weeks post-therapy start
Other	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
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.	Baseline to up to 6 weeks
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.	Baseline to up to 6 weeks
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.	1 to 6 weeks post-therapy start
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.	Baseline to up to 6 weeks
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.	Baseline to up to 6 weeks
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	Baseline
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	Baseline
Secondary	Baseline Standardized Uptake Values (SUV) by FLT PET	FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET	Baseline
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	1 to 6 weeks post-therapy start
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	1 to 6 weeks post-therapy start
Secondary	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