NCT02455453

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_2 breast-cancer

Timeline
Completed

Started Apr 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 28, 2015

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

May 14, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 27, 2015

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 3, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 3, 2019

Completed
1 year until next milestone

Results Posted

Study results publicly available

January 14, 2020

Completed
Last Updated

January 14, 2020

Status Verified

January 1, 2020

Enrollment Period

3.7 years

First QC Date

May 14, 2015

Results QC Date

December 16, 2019

Last Update Submit

January 13, 2020

Conditions

Outcome Measures

Primary Outcomes (2)

  • Change in Primary Tumor FFNP Uptake Before and After Estradiol Challenge as Measured by Percent Change in Standardized Uptake Value (SUV)

    Completion of second FFNP-PET/CT scan (up to 4 weeks)

  • Change in Secondary Tumor FFNP Uptake Before and After Estradiol Challenge as Measured by Percent Change in Standardized Uptake Value (SUV)

    Completion of second FFNP-PET/CT scan (up to 4 weeks)

Secondary Outcomes (1)

  • Heterogeneity of Tumor FFNP Uptake as Measured by Number of Participants With Heterogenous Response

    Completion of second FFNP-PET/CT scan (up to 4 weeks)

Study Arms (1)

Diagnostic FFNP-PET/CT Scan

EXPERIMENTAL

* (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.

Drug: 18F-FFNPDevice: CTI/Siemens Biograph 40 PET/CT ScannerDrug: EstradiolDrug: 18F-FDG

Interventions

Also known as: 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione
Diagnostic FFNP-PET/CT Scan

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

Diagnostic FFNP-PET/CT Scan
Diagnostic FFNP-PET/CT Scan
Diagnostic FFNP-PET/CT Scan

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • +5 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Interventions

EstradiolFluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

EstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsDeoxyglucoseDeoxy SugarsCarbohydrates

Results Point of Contact

Title
Farrokh Dehdashti, M.D.
Organization
Washington University School of Medicine

Study Officials

  • Farrokh Dehdashti, M.D.

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

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

Study Record Dates

First Submitted

May 14, 2015

First Posted

May 27, 2015

Study Start

April 28, 2015

Primary Completion

January 3, 2019

Study Completion

January 3, 2019

Last Updated

January 14, 2020

Results First Posted

January 14, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Locations