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

Not Applicable

Completed

Conditions: Stage IIIA Breast Cancer
Stage IB Breast Cancer
Stage IIB Breast Cancer
Estrogen Receptor Positive
Stage IA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
HER2/Neu Negative
Male Breast Carcinoma
Stage IIA Breast Cancer

Interventions: Drug: Fluorothymidine F-18
Procedure: Positron Emission Tomography
Other: Laboratory Biomarker Analysis
Drug: Run-in (short pre-surgery course) of endocrine-targeted therapy

Registration Number: NCT01928186

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (FLT PET)	Fluorothymidine F-18	Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
Diagnostic (FLT PET)	Positron Emission Tomography	Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
Diagnostic (FLT PET)	Laboratory Biomarker Analysis	Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.
Diagnostic (FLT PET)	Run-in (short pre-surgery course) of endocrine-targeted therapy	Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.

Primary Outcome Measures

Name	Time	Method
Percent Change in Net Influx Constant (Ki) by FLT PET	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.
Percent Change in SUV by FLT PET	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.
Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample	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.
Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens	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

Name	Time	Method
Post-treatment Standardized Uptake Values (SUV) by FLT PET	1 to 6 weeks post-therapy start	FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET
Percentage Change in K1 (Blood Flow Parameter) by FLT PET	Baseline to up to 6 weeks	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	Baseline	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	Baseline	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	Baseline	FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET
Post-therapy Ki (Flux Constant) Values by FLT PET	1 to 6 weeks post-therapy start	Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET
Post-treatment FLT Transport (K1) Values by FLT PET	1 to 6 weeks post-therapy start	K1 (blood flow measure) in breast tumor tissue as determined by the post-therapy FLT PET