Clinical trial NCT02955394: Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
Official title: Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER+/Her2 - breast cancer
Preoperative Fulvestrant
Enzalutamide
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2016-11-04
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With a PEPI Score Equal to Zero at Post Treatment
timeFrame: 16 Weeks
Secondary outcomes:
measure: Disease-free Survival
timeFrame: 15 months
measure: Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate
timeFrame: 4 years
measure: Androgen Receptor (AR) Expression
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
Study officials:
affiliation: University of Colorado, Denver
name: Anthony D Elias, MD
role: PRINCIPAL_INVESTIGATOR
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