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

Phase 2

Active, not recruiting

Brief Summary: 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.

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Fulvestrant Without Enzalutamide	Fulvestrant	500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Fulvestrant With Enzalutamide	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.
Fulvestrant With Enzalutamide	Fulvestrant	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients With a PEPI Score Equal to Zero at Post Treatment	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.

Secondary Outcome Measures

Name	Time	Method
Disease-free Survival	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.
Androgen Receptor (AR) Expression	16 Weeks	The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.
Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate	4 years	To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects.

Locations (3): Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
West Cancer Center
🇺🇸
Germantown, Tennessee, United States
University of Colorado
🇺🇸
Aurora, Colorado, United States