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Neoadjuvant Darolutamide Alone or in Combination With Standard Therapy for Stage II-IIIA, AR+, TNBC

ConditionsAnatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Triple-Negative Breast Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVandana Abramson

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

<10% staining for estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemistry (IHC)

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Breast Biopsy Procedure

    Procedure/Surgery

    Undergo breast biopsies

  • Carboplatin

    Drug

    Given IV

  • Cyclophosphamide

    Drug

    Given IV

  • Darolutamide

    Drug

    Given PO

  • Doxorubicin

    Drug

    Given IV

  • Epirubicin

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Paclitaxel

    Drug

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Surgical Procedure

    Procedure/Surgery

    Undergo breast surgery

  • Ultrasound Imaging

    Procedure/Surgery

    Undergo US

Treatment groups

51 Participants
are divided into 2 treatment groups
Group A: Arm A (Standard chemotherapy + immunotherapy)Active comparator 11 interventions
Group B: Arm B (Standard chemotherapy + immunotherapy + darolutamide)Experimental treatment 12 interventions

Trial outcomes

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.

Time frame
Baseline up to 5 years

Secondary outcomes

1

Association between ΔKi-67 level and pathologic complete response rate (pCR) status

The exact 95% CIs for pCR will be reported. The generalized linear model will be used to study the correlation between changes of the Ki-67 level and pCR status. In addition, the generalized linear model will be applied to test the correlation between post treatment Ki-67 level and pCR status.

Time frame
Baseline up to 5 years
2

Overall response rate (ORR)

Will be estimated using the Kaplan-Meier method with 95% CIs.

Time frame
From registration to disease progression or death due to any cause, assessed up to 5 years
3

Event-free survival (EFS)

Will be estimated using the Kaplan-Meier method with 95% CIs. The CI based on the Greenwood's variance will be reported. In addition, the two treatment arms as well as the possible risk factors will be compared for survival using the log-rank test. For the multivariable analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age of disease onset, on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% CI will be reported.

Time frame
From registration to disease progression or death due to any cause, assessed up to 5 years
4

Correlation of change in Ki-67 with pCR rates and EFS

The exact 95% CIs for pCR will be reported. The generalized linear model will be used to study the correlation between changes of the Ki-67 level and pCR status. In addition, the investigators will apply the generalized linear model to test the correlation between post treatment Ki-67 level and pCR status. The study survival will be estimated using the Kaplan-Meier method with 95% CIs. The CI based on the Greenwood's variance will be reported.

Time frame
At 2 weeks and 6 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Vandana Abramson

Lead sponsor

Vanderbilt-Ingram Cancer Center

Sponsor institution

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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