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

NCT01928186 | Completed Results

• 4 other identifiers: 7536NCI-2013-01380P30CA015704RC1CA146456
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (7)

• Percentage Change in K1 (Blood Flow Parameter) by FLT PET

  Baseline to up to 6 weeks

• Baseline Ki (Flux Constant) Values by FLT PET

  Baseline

• Baseline FLT Transport (K1) Values by FLT PET

  Baseline

• Baseline Standardized Uptake Values (SUV) by FLT PET

  Baseline

• Post-therapy Ki (Flux Constant) Values by FLT PET

  1 to 6 weeks post-therapy start

Other Outcomes (2)

• Post-treatment Gene Expression Levels

  1 to 6 weeks post-therapy start

• Pre-treatment Gene Expression Levels

  Baseline

Study Arms (1)

Diagnostic (FLT PET)

EXPERIMENTAL

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

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

Interventions

Fluorothymidine F-18 DRUG

Undergo FLT PET

Also known as: 18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine

Diagnostic (FLT PET)

Positron Emission Tomography PROCEDURE

Undergo FLT PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

Diagnostic (FLT PET)

Laboratory Biomarker Analysis OTHER

Correlative studies

Diagnostic (FLT PET)

Run-in (short pre-surgery course) of endocrine-targeted therapy DRUG

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.

Diagnostic (FLT PET)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

alovudine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Dr. Hannah Linden
• Organization: University of Washington / Seattle Cancer Care Alliance

hmlinden@uw.edu

206-288-6989

Study Officials

• Hannah Linden

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: August 23, 2013
• Study Start: September 1, 2011
• Primary Completion: July 20, 2015
• Study Completion: July 20, 2015
• Last Updated: May 15, 2018
• Results First Posted: September 25, 2017

Record last verified: 2018-04

Locations

US (1)