Assessment of Functional Status of Estrogen Receptors in Breast Cancer by Positron Emission Tomography

NCT ID: NCT02455453

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-28
• Study Completion Date: 2019-01-03

Brief Summary

The purpose of this study is to evaluate the uptake of a radioactive tracer 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (FFNP) uptake, which binds to breast cancer progesterone receptors (PgRs) on a PET/CT scan before and after administration of estradiol for one day (estrogen challenge) to determine if the change in uptake is a predictor of response to endocrine therapy (ET) in patients with hormone-sensitive estrogen receptor positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Estradiol is the most potent of the naturally occurring estrogens, and can be administered to treat menopausal symptoms and also sometimes to treat metastatic breast cancer. The investigators propose to study patients with biopsy-proven newly diagnosed, locally advanced, metastatic, or recurrent breast cancer who are going to be treated with endocrine therapy (ET) (tamoxifen,aromatase inhibitors or fulvestrant as standard of care therapy.

Subjects will undergo a total of two FFNP-PET/CT scans; one before and a second one immediately following the one day estradiol challenge before the start of standard of care ET. The estradiol challenge will consist of administering a total of 6 mg of estradiol orally (three doses of 2 mg each) given at approximately 8 hour intervals and over a 24 hour period.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Diagnostic FFNP-PET/CT Scan

• (2) 18F-FFNP-PET/CT scans

• First one prior to estradiol challenge test
• Second one immediately following one day of estradiol challenge test
• (1) FDG-PET/CT scan at screening
• The estradiol challenge test will consist of administering a total of 6 mg of estradiol dosed orally as three 2 mg tablets with each tablet being administered approximately 8 hours apart and within a 24 hour period. This estradiol medication will be provided to the patient by the study.

Group Type: EXPERIMENTAL

18F-FFNP

Intervention Type: DRUG

CTI/Siemens Biograph 40 PET/CT Scanner

Intervention Type: DEVICE

• Will include (1) 18-FDG-PET/CT scan
• Will include (2) 18F-FFNP-PET/CT scans

Estradiol

Intervention Type: DRUG

18F-FDG

Intervention Type: DRUG

Interventions

18F-FFNP

Intervention Type: DRUG

CTI/Siemens Biograph 40 PET/CT Scanner

• Will include (1) 18-FDG-PET/CT scan
• Will include (2) 18F-FFNP-PET/CT scans

Intervention Type: DEVICE

Estradiol

Intervention Type: DRUG

18F-FDG

Intervention Type: DRUG

Other Intervention Names

21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione

Eligibility Criteria

Inclusion Criteria

• Patient must be postmenopausal defined as meeting one or more of the following:

• Age ≥ 60 years
• Amenorrheic for at least 12 months
• Surgically sterile- having undergone bilateral oophorectomy,
• FSH level in postmenopausal range according to institutional standards (note follicle-stimulating hormone (FSH) laboratory testing must be ordered as standard of care to determine optimal treatment and should not be ordered simply to confirm eligibility to this study)
• OR Pre-menopausal for whom standard estradiol treatment (ET) is planned with ovarian suppression (imaging on study should be completed prior to start of ovarian suppression)
• Patient must have histological or cytological confirmed breast cancer and fall into one of the following categories:

• New diagnosis with plans for at least 6 months of neoadjuvant ET or any amount of neoadjuvant ET if surgery is planned as this will be used for response assessment .
• Patients with newly diagnosed metastatic breast cancer or patient with known metastatic disease who has progressed while on therapy (no washout period is needed if the patient was treated with AIs or chemotherapy, but 2 months washout period is needed if the patient was treated with tamoxifen) who are going to be treated with ET.
• Patient must have any one of the following types of breast cancer (primary or metastatic): ER+/PgR+/HER2- or ER+/PgR-/HER2-.

• ER+ is defined as Allred score of at least 4 and greater.
• PgR+ is defined as Allred score of at least 4 and greater.
• Immunohistochemistry (IHC) is the primary assay methodology for HER2. HER2- refers to HER2 of 0, 1+ by IHC or negative by fluorescence in situ hybridization (FISH)
• Patient must have at least one measurable lesion according to RECIST 1.1 by radiological evaluation (ultrasound, mammography, MRI, CT, PET) or physical examination.

• Patients with evaluable osseous metastasis that are lytic or mixed lytic-sclerotic are eligible.
• Patients with hepatic lesions may be eligible provided the location of the lesion is peripheral or not too close to hepatic ducts. Decision on hepatic lesion eligibility will be made by the principal investigator or sub-investigator after careful review of all available imaging to ensure evaluation of the lesion will not be obscured by normal hepatobiliary excretion of 18F-FFNP.
• Patient must be able to understand and willing to sign a written informed consent document.
• Prior chemotherapy or endocrine therapy is allowed
• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or, based on the judgment of the treating medical oncologist, can tolerate imaging and at least 6 months of ET
• The patient should have a life expectancy of > 6 months.

Exclusion Criteria

• Patient with other invasive malignancies, with the exception of non-melanoma skin cancer or cervical carcinoma in-situ, who had (or have) any evidence of the other cancer present within the last 5 years
• Unable to tolerate up to 60 min of PET imaging per imaging session.
• Patients with non-measurable non-evaluable lesions such as pleural effusion are not eligible to participate.
• Patients with vertebral lesions that, in the opinion of the Principal Investigator and the treating medical oncologist, pose an imminent risk for cord compression.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Farrokh Dehdashti, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Dehdashti F, Wu N, Ma CX, Naughton MJ, Katzenellenbogen JA, Siegel BA. Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. Nat Commun. 2021 Feb 2;12(1):733. doi: 10.1038/s41467-020-20814-9.

Reference Type: DERIVED

PMID: 33531464 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

5R01CA195450-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201411005

Identifier Type: -

Identifier Source: org_study_id