Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

May 23, 2023 updated by: University of Colorado, Denver

Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after ~4 months on treatment.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after ~4 months on treatment. After consent, all patients will get a tissue biopsy, and than half the patients will get fulvestrant alone (standard dosing) and the other half of the patients will get fulvestrant plus enzalutamide. At ~4 weeks, a biopsy will be done and therapy will be continued. Hormone therapy will continue for ~4 months at which point the patients will undergo surgical resection.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 101 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ER+ Her2- breast cancer
  • Stage at least T2 or greater
  • Planned to get local surgery
  • Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression.
  • At least 18 years of age
  • Not on anticoagulants
  • PS 0-2
  • Able to swallow study drug and comply with study requirements
  • ANC >1000/uL, platelets >75,000/uL at screening visit
  • Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or < 5 times ULN if patient has documented liver metastases
  • Creatinine < 1.5 times ULN
  • INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy
  • Willing to donate blood for research at 4 time points
  • Willing to undergo core biopsies for research at study entry and at ~4 weeks.
  • Willing to donate tissue to research from the surgical specimen
  • Written informed consent obtained prior to biopsies and blood samples

Exclusion Criteria:

  • Current or previously treated brain or leptomeningeal metastases
  • History of seizures
  • Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464).
  • Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal estrogens are allowed if necessary for patient comfort.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Fulvestrant Without Enzalutamide
500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Drug: Fulvestrant
500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Other Names:
  • FASLODEX
Experimental: Fulvestrant With Enzalutamide
500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC), plus160mg of Enzalutamide will be given daily.
Drug: Fulvestrant
500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Other Names:
  • FASLODEX
Drug: Enzalutamide
160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
Other Names:
  • MDV3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With a PEPI Score Equal to Zero at Post Treatment
Time Frame: 16 Weeks

The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence.

PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and >= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better.
16 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Survival
Time Frame: 15 months
Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
15 months
Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate
Time Frame: 4 years
To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects.
4 years
Androgen Receptor (AR) Expression
Time Frame: 16 Weeks
The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.
16 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Anthony D Elias, MD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2017

Primary Completion (Actual)

February 17, 2023

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

November 1, 2016

First Submitted That Met QC Criteria

November 2, 2016

First Posted (Estimated)

November 4, 2016

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-1042.cc

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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