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Fulvestrant with or without Enzalutamide in Treating Patients with Estrogen Receptor Positive and HER2 Negative Breast Cancer

Trial Status: Active

This randomized phase II trial studies how well fulvestrant with or without enzalutamide works in treating patients with estrogen receptor positive and HER2 negative breast cancer. Drugs used in chemotherapy, such as fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Androgen can cause the growth of breast cancer cells. Hormone therapy using enzalutamide may fight breast cancer by blocking the use of androgen by the tumor cells. Giving fulvestrant and enzalutamide may work better in treating patients with breast cancer.

Inclusion Criteria

  • Estrogen receptor (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; pre- or peri- menopausal subjects must have a negative urine pregnancy test confirmed at screening
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Able to swallow study drug and comply with study requirements
  • Absolute neutrophil count (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 (e.g., 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
  • International normalization ratio (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
  • Agreement to exercise appropriate use of contraception. Subjects should use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at the time of screening for an enzalutamide study and continuing throughout the course of treatment and for at least three months after enzalutamide is discontinued

Exclusion Criteria

  • Current or previously treated brain or leptomeningeal metastases
  • History of seizures
  • Prior treatment with an anti-androgen (abiraterone, apalutamide [ARN-509], bicalutamide, enzalutamide, AR antagonist ODM-201 [ODM-201], TAK-448, TAK-683, orteronel [TAK-700], seviteronel [VT-464])
  • Systemic estrogens or androgens within 14 days before initiating therapy; vaginal estrogens are allowed if necessary for patient comfort
  • Not on full dose anticoagulants


University of Colorado Hospital
Status: ACTIVE
Contact: Anthony David Elias
Phone: 720-848-1030

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Monica N. Fornier
Phone: 646-888-4563


The West Clinic - Wolf River
Status: ACTIVE
Contact: Anthony David Elias
Phone: 720-848-1030


I. Evaluate the rate of Preoperative Endocrine Prognostic Index (PEPI) score equal to 0 at 16 weeks post treatment for each of the two treatment arms separately.


I. To determine the percentage of progression-free survival (PFS), clinical response rate (by physical exam and breast imaging) after 16 weeks of therapy for the single drug arm and combination of enzalutamide/fulvestrant arm separately.

II. To assess the association between PEPI score and the clinical outcomes such as PFS and clinical response for all the subjects.

III. To confirm the safety profile of the combination.

IV. To determine the extent of androgen receptor (AR) expression and signaling in breast tissue, to evaluate the effect of the drug(s) on the tumor, and to evaluate the relationship of these effects on clinical outcomes for the two arms separately.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 28 of course 1 and every 4 weeks of subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive fulvestrant as in Arm A and enzalutamide orally (PO) once daily (QD). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 6 months for 2 years, and then yearly for 3 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Colorado Hospital

Principal Investigator
Anthony David Elias

  • Primary ID 16-1042
  • Secondary IDs NCI-2017-00784
  • ID NCT02955394