Neoadjuvant Darolutamide Alone or in Combination With Standard Therapy for Stage II-IIIA, AR+, TNBC
A Phase II Neoadjuvant Clinical Trial of the Androgen Receptor Inhibitor Darolutamide in Early-Stage Androgen Receptor Positive (AR+) Triple-Negative Breast Cancer
3 other identifiers
interventional
51
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2025
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2025
CompletedFirst Posted
Study publicly available on registry
June 11, 2025
CompletedStudy Start
First participant enrolled
September 9, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2033
October 30, 2025
October 1, 2025
3 years
June 3, 2025
October 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Mean ΔKi-67 level
The two-sample t-test as well as the Wilcoxon Rank-Sum test will be applied to examine the magnitude of ΔKi-67 between the two study arms. The 95% confidence interval (CI) of the mean difference of ΔKi-67 level between two treatment arms will be reported.
Baseline up to 5 years
Secondary Outcomes (6)
Association between ΔKi-67 level and pathologic complete response rate (pCR) status
Baseline up to 5 years
Overall response rate (ORR)
From registration to disease progression or death due to any cause, assessed up to 5 years
Event-free survival (EFS)
From registration to disease progression or death due to any cause, assessed up to 5 years
Correlation of change in Ki-67 with pCR rates and EFS
At 2 weeks and 6 months
Monitor circulating tumor DNA throughout study to correlate with disease response
Baseline up to 5 years
- +1 more secondary outcomes
Study Arms (2)
Arm A (Standard chemotherapy + immunotherapy)
ACTIVE COMPARATORPatients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 4 cycles (cycles 1-4) in the absence of disease progression or unacceptable toxicity. Then, patients receive pembrolizumab IV over 30 minutes, cyclophosphamide IV, and doxorubicin IV or epirubicin IV on day 1 of subsequent cycles. Cycles repeat every 21 days for up to an additional 4 cycles (cycles 5-8) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery on study, as well as US or MRI, blood sample collection, and breast biopsies throughout the study.
Arm B (Standard chemotherapy + immunotherapy + darolutamide)
EXPERIMENTALPatients receive darolutamide PO BID for 14 days in the absence of disease progression or unacceptable toxicity. Patients then receive darolutamide PO BID, pembrolizumab IV over 30 minutes on day 1 of each cycle, and paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 4 cycles (cycles 1-4) in the absence of disease progression or unacceptable toxicity. Then, patients receive pembrolizumab IV over 30 minutes, cyclophosphamide IV, and doxorubicin IV or epirubicin IV on day 1 of subsequent cycles. Cycles repeat every 21 days for up to an additional 4 cycles (cycles 5-8) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery on study, as well as US or MRI, blood sample collection, and breast biopsies throughout the study.
Interventions
Undergo blood sample collection
Undergo breast biopsies
Given IV
Given IV
Given PO
Given IV
Given IV
Undergo MRI
Given IV
Given IV
Undergo breast surgery
Undergo US
Eligibility Criteria
You may qualify if:
- 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: defined as ≥ 80% staining for AR by IHC
- Primary tumor clinically or radiographically ≥ 1cm in size or stage II-IIIA and eligible for neoadjuvant treatment
- Absolute neutrophil count (ANC) ≥ 1500/µL (≤ 28 days prior to first dose of protocol-indicated treatment)
- Platelets ≥ 100,000/µL (≤ 28 days prior to first dose of protocol-indicated treatment)
- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (≤ 28 days prior to first dose of protocol-indicated treatment)
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants at the site) (≤ 28 days prior to first dose of protocol-indicated treatment)
- Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), or direct bilirubin ≤ ULN for participants with total bilirubin \> 1.5 x ULN (≤ 28 days prior to first dose of protocol-indicated treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 times institutional upper limit of normal (ULN) (≤ 28 days prior to first dose of protocol-indicated treatment)
- Calcium ≤ 11.5 mg/dL or ≤ 2.9 mmol/L; in patients with albumin outside the normal range, calcium (corrected for albumin) must be ≤ 11.5 mg/dL or ≤ 2.9 mmol/L (≤ 28 days prior to first dose of protocol-indicated treatment)
- +4 more criteria
You may not qualify if:
- Non-resectable breast cancer as assessed by the primary treating surgeon or evidence of metastatic disease
- Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
- Patient is pregnant or breastfeeding
- Patients with moderate hepatic impairment (Child-Pugh Class B cirrhosis or higher)
- Is currently participating in or within four weeks prior to receiving first dose of study treatment in a study of an investigational agent or investigational device
- Participants who have entered the follow-up phase of an investigational study may participate as long as it has been four weeks after the last dose or last exposure to the previous investigational agent or investigational device
- Recipient of previous allogeneic tissue/solid organ transplant
- Known severe hypersensitivity (≥ Grade 3) to study drug, pembrolizumab, carboplatin, doxorubicin/epirubicin, paclitaxel, or cyclophosphamide and/or any of the excipients of these drugs
- History of myocarditis or pericarditis or other known underlying heart disease that is clinically significant by investigator judgment (for example, cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III or IV, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction). History of cerebrovascular accident (including transient ischemic attack \[TIA\]) within the past six months (24 weeks) prior to starting study treatment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection/sepsis, or psychiatric illness/social situations that would limit compliance with study requirements
- Known conditions that would preclude the use of checkpoint inhibitors
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Vandana Abramsonlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Vandana G Abramson
Vanderbilt University/Ingram Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 3, 2025
First Posted
June 11, 2025
Study Start
September 9, 2025
Primary Completion (Estimated)
September 1, 2028
Study Completion (Estimated)
October 1, 2033
Last Updated
October 30, 2025
Record last verified: 2025-10