Clinical trial NCT01928186: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-08-23
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Percent Change in Net Influx Constant (Ki) by FLT PET
timeFrame: Baseline to up to 6 weeks
measure: Percent Change in SUV by FLT PET
timeFrame: Baseline to up to 6 weeks
measure: Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample
timeFrame: 1 to 6 weeks post-therapy start
measure: Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens
timeFrame: Baseline to up to 6 weeks
Secondary outcomes:
measure: Percentage Change in K1 (Blood Flow Parameter) by FLT PET
timeFrame: Baseline to up to 6 weeks
measure: Baseline Ki (Flux Constant) Values by FLT PET
timeFrame: Baseline
measure: Baseline FLT Transport (K1) Values by FLT PET
timeFrame: Baseline
measure: Baseline Standardized Uptake Values (SUV) by FLT PET
timeFrame: Baseline
measure: Post-therapy Ki (Flux Constant) Values by FLT PET
timeFrame: 1 to 6 weeks post-therapy start
measure: Post-treatment FLT Transport (K1) Values by FLT PET
timeFrame: 1 to 6 weeks post-therapy start
measure: Post-treatment Standardized Uptake Values (SUV) by FLT PET
timeFrame: 1 to 6 weeks post-therapy start
Other outcomes:
measure: Post-treatment Gene Expression Levels
timeFrame: 1 to 6 weeks post-therapy start
measure: Pre-treatment Gene Expression Levels
timeFrame: Baseline
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Hannah Linden
role: PRINCIPAL_INVESTIGATOR
References: