F-18 16 Alpha-Fluoroestradiol-Labeled Positron Emission Tomography in Predicting Response to First-Line Hormone Therapy in Patients With Stage IV Breast Cancer

NCT00602043 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-00270IRB #6590CDR0000584077UWCC-65908052
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well F-18 16 alpha-fluoroestradiol (FES) imaging works in predicting response to first-line hormone therapy in women with hormone receptor-positive metastatic breast cancer. Diagnostic procedures, such as FES imaging, may help predict how well patients will respond to hormone therapy and may help plan the best treatment.

Conditions

Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  Patients were expected to start endocrine therapy within 2 weeks of the FES PET scan. Response assessment was evaluated at 3 and 6 months. For patients with at least one site of measurable disease \[per response evaluation criteria in solid tumors (RECIST, version 1.1)\], size-based response criteria were used to assess response. For patients without disease evaluable by RECIST 1.1, largely patients with bone-dominant metastatic breast cancer, serial FDG PET scanning was used to determine response. A decline in the FDG PET SUV (standard uptake value) of 30% or more was considered as response and an increase of 20% or more was considered to be progressive disease (PD). The initial (baseline) FES uptake was compared to clinical benefit (PD versus other outcome at 6 months).

  Up to 6 months

Secondary Outcomes (3)

• Number of Participants With Clinical Benefit

  Up to 6 months

• Time to Progression

  Up to 6 months

• Correlation of FES Uptake With ER Assays

  Up to 6 months

Study Arms (1)

Diagnostic (FES)

EXPERIMENTAL

Patients undergo \[\^18F\] FES PET scan. Patients also undergo standard clinical fludeoxyglucose F 18 (FDG)-PET or FDG-PET/CT scan up to 14 days prior to \[\^18F\] FES PET scan.

Radiation: F-18 16 alpha-fluoroestradiol; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Procedure: computed tomography; Other: laboratory biomarker analysis

Interventions

F-18 16 alpha-fluoroestradiol RADIATION

Undergo \[\^18F\] FES PET

Also known as: F-18 FES, fluorine-18 16 alpha-fluoroestradiol

Diagnostic (FES)

fludeoxyglucose F 18 RADIATION

Undergo standard clinical FDG PET/CT

Also known as: 18FDG, FDG

Diagnostic (FES)

positron emission tomography PROCEDURE

Undergo \[\^18F\] FES PET

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Diagnostic (FES)

computed tomography PROCEDURE

Undergo standard clinical FDG PET/CT

Also known as: tomography, computed

Diagnostic (FES)

laboratory biomarker analysis OTHER

Correlative studies

Diagnostic (FES)

Eligibility Criteria

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

You may qualify if:

• Patients will have pathologically confirmed invasive breast cancer with clinical, radiographic and/or pathologic evidence of stage IV disease; patients must have tissue blocks available from biopsy of at least one site of metastatic disease and/or from diagnosis of their primary breast cancer
• Disease may be measurable (by Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) or non-measurable but must be present in at least one non-liver site and imageable on FDG PET scan; in patients with non-measurable disease by RECIST criteria, one of the following may be used to assess and follow disease: MUC-1 antigen level (either cancer antigen \[CA\] 27.29 or carcinoembryonic antigen \[CEA\]) \> 2 x upper limit of normal (ULN), Circulating tumor cell assay \> 5, or FDG-PET SUV \> 2.5 in purely lytic lesions; elevated tumor markers alone are insufficient
• No prior endocrine therapy for breast cancer or
• Off adjuvant endocrine therapy for \> 6 months or
• Greater than 2 years of a single adjuvant endocrine therapy at the time of first recurrence and plan to change to alternate endocrine therapy; use of tamoxifen must be discontinued 6-8 weeks prior to entrance into the study
• Prior chemotherapy regimens in the adjuvant or neoadjuvant setting are allowed
• Women treated with adjuvant LHRH (luteinizing hormone-releasing hormone) analog are eligible
• Be assessed for menopausal status; 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
• Premenopausal patients must have a baseline FSH, and estradiol levels to determine menopausal status; measures will be repeated at 3-6 months to confirm menopausal status
• Patients must be positive for estrogen receptor (ER) and may or may not be positive for progesterone receptor (PgR) by IHC in the primary tumor and/or metastatic site; the pathology report for assay of ER will be reviewed by one of the investigators prior to enrollment, the study pathologist will review the pathology report if necessary for determination of study eligibility
• Tumor HER2/neu expression must be determined prior to study enrollment; assessment may be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry (ICC); if determination is intermediate by ICC, FISH must be performed

You may not qualify if:

• Patients with a history of prior endocrine therapy for metastatic disease are NOT eligible; adjuvant endocrine therapy for \< 2 years total or discontinued less than 6 months before first disease recurrence also excludes the patient
• Patients with disease in the liver only are NOT eligible for the study
• Patients who are HER2/neu positive disease and planning to undergo HER2-directed therapy (trastuzumab or lapatinib) are NOT eligible for the study
• Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded
• Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases
• History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent
• Any other life-threatening illness (e.g., serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication)
• Unwillingness to give informed consent
• Medically unstable as judged by the patient's physician
• Psychological, familial, sociological, or geographical conditions which do not permit compliance with the study protocol
• Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals; patients with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion
• Patient weight greater than 400 lbs (exceeds weight limit for tomograph table)
• Uncontrolled diabetes mellitus (fasting glucose \> 200 mg/dL)
• Adult patients who require monitored anesthesia for PET scanning

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Peterson LM, Kurland BF, Schubert EK, Link JM, Gadi VK, Specht JM, Eary JF, Porter P, Shankar LK, Mankoff DA, Linden HM. A phase 2 study of 16alpha-[18F]-fluoro-17beta-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol. 2014 Jun;16(3):431-40. doi: 10.1007/s11307-013-0699-7. Epub 2013 Oct 30.

  PMID: 24170452 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Dr. David Mankoff
• Organization: University of Pennsylvania

david.mankoff@uphs.upenn.edu

(2015) 615-3687

Study Officials

• Janet F Eary, MD

  Department of Radiology, University of Alabama, Birmingham, AL

  PRINCIPAL INVESTIGATOR

• David A Mankoff, MD, PhD

  University of Pennsylvania

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: January 28, 2008
• Study Start: September 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: September 1, 2014
• Last Updated: February 19, 2020
• Results First Posted: December 25, 2014

Record last verified: 2020-02

Locations

US (1)