Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| 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:
|
| 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: Enzalutamide
160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
Other Names:
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:
|
Outcome Measures
Primary Outcome Measures
- Document the number of patients in both treatment arms separately who have a PEPI score equal to 0 at post treatment [16 Weeks]
The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy.
Secondary Outcome Measures
- Progression-free survival (PFS) [16 Weeks]
To determine the percentage of progression-free survival (PFS) (complete and partial response plus stable disease) for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
- Correlate PEPI score and Progression-free survival, Clinical Benefit Rate, and Overall Response Rate [16 Weeks]
To assess the association between PEPI score and the clinical, outcomes such as PFS, ORR, clinical benefit for all subjects.
- Androgen Receptor (AR) expression [16 Weeks]
Nuclear AR expression and AR pathway expression correlation with clinical outcomes. AR expression is associated with resistance to anti-estrogen therapy. Its blockade may enhance response.
- Clinical Benefit Rate [16 weeks]
To determine the percentage of clinical benefit rate (complete and partial response plus stable disease) for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
ER+ Her2- breast cancer
-
Stage at least T2 or greater
-
Planned to get local surgery
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Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression.
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At least 18 years of age
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Not on anticoagulants
-
PS 0-2
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Able to swallow study drug and comply with study requirements
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ANC >1000/uL, platelets >75,000/uL at screening visit
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Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease)
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or < 5 times ULN if patient has documented liver metastases
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Creatinine < 1.5 times ULN
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INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy
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Willing to donate blood for research at 4 time points
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Willing to undergo core biopsies for research at study entry and at ~4 weeks.
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Willing to donate tissue to research from the surgical specimen
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Written informed consent obtained prior to biopsies and blood samples
Exclusion Criteria:
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Current or previously treated brain or leptomeningeal metastases
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History of seizures
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Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464).
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Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal estrogens are allowed if necessary for patient comfort.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Colorado | Aurora | Colorado | United States | 80045 |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 3 | West Cancer Center | Germantown | Tennessee | United States | 38138 |
Sponsors and Collaborators
- University of Colorado, Denver
- United States Department of Defense
Investigators
- Principal Investigator: Anthony D Elias, MD, University of Colorado, Denver
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 16-1042.cc