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

University of Colorado Denver (CU Denver)

Status and phase: Active, not recruiting; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Enzalutamide; Drug: Fulvestrant

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02955394

16-1042.cc

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: Female

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 2 patient groups, including a placebo group

Fulvestrant Without Enzalutamide

Placebo Comparator group

Description:

500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)

Treatment:

Drug: Fulvestrant

Fulvestrant With Enzalutamide

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: Enzalutamide