A Phase II Neoadjuvant Clinical Trial of the Androgen Receptor Inhibitor Darolutamide in Early-Stage Androgen Receptor Positive (AR+) Triple-Negative Breast Cancer
Vandana Abramson
Summary
This phase II trial compares the effect of adding darolutamide to standard therapy versus standard therapy alone before surgery for the treatment of patients with stage II-IIIA androgen receptor positive triple-negative breast carcinoma. Standard therapy before surgery for triple-negative breast cancer typically consists of a combination of chemotherapy and immunotherapy drugs. Chemotherapy drugs, such as carboplatin, paclitaxel, doxorubicin and cyclophosphamide, 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving darolutamide in combination with standard therapy before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed.
Description
PRIMARY OBJECTIVE: I. To compare the mean ΔKi-67 level between the darolutamide therapy arm and the control arm. SECONDARY OBJECTIVES: I. To determine the pathologic complete response rate (pCR) and overall response rate (ORR) in patients on the darolutamide and control arms. II. To determine event-free survival (EFS) in patients with androgen receptor positive (AR+) breast cancer in both arms. III. To correlate the change in Ki-67 at 2 weeks and 6 months with pCR rates and EFS in patients with AR+ breast cancer in both arms. IV. To monitor circulating tumor deoxyribonucleic acid (ctDNA)…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Signed and dated written informed consent as well as the ability to understand and the willingness to sign written consent prior to study registration * Male or female ≥ 18 years of age on the day of signing informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically confirmed newly diagnosed breast cancer with the following requirements: * \<10% staining for estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemistry (IHC) * HER2 negative by fluorescence in situ hybridization (FISH) * AR positive: d…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBreast Biopsy Procedure
Undergo breast biopsies
- DrugCarboplatin
Given IV
- DrugCyclophosphamide
Given IV
- DrugDarolutamide
Given PO
- DrugDoxorubicin
Given IV
- DrugEpirubicin
Given IV
Location
- Vanderbilt University/Ingram Cancer CenterNashville, Tennessee