Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if enzalutamide is safe and effective in the treatment of patients with advanced breast cancer that express the androgen receptor but do not express the estrogen or progesterone receptor and are not Her2 amplified.

Official Title
-----------------
A PHASE 2, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY OF THE CLINICAL ACTIVITY AND SAFETY OF ENZALUTAMIDE IN PATIENTS WITH ADVANCED, ANDROGEN RECEPTOR-POSITIVE, TRIPLE-NEGATIVE BREAST CANCER

Conditions
-----------------
Advanced, Androgen Receptor Positive Triple Negative Breast Cancer

Intervention / Treatment
-----------------
* Drug: Enzalutamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women at least 18 years of age; Advanced AR+ TNBC; Availability of a representative tumor specimen: Either measurable disease or bone only nonmeasurable disease; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: Any severe concurrent disease, infection, or comorbid condition; Any condition or reason that interferes with the patient's ability to participate in the trial, that may cause undue risk, or complicates the interpretation of safety data; Current or previously treated brain metastasis or active leptomeningeal disease; Current hormone replacement therapy; Local palliative radiation therapy within 7 days before day 1; History of another invasive cancer within 5 years of day 1; Absolute neutrophil count < 1500/µL, platelet count < 75,000/µL, or hemoglobin < 9 g/dL (5.6 mmol/L) at the screening visit; Creatinine > 1.5 times upper limit of normal (ULN) at the screening visit; History of seizure or any condition that may predispose to seizure; Clinically significant cardiovascular disease; Active gastrointestinal disorder affecting absorption; Major surgery within 4 weeks before day 1; Treatment with any commercially available anticancer agent within 14 days before day 1; Treatment with any investigational agent within 2 weeks before day 1; Treatment with any of the following medications within 2 weeks before day 1: Estrogens, including hormone replacement therapy; Androgens (testosterone, dihydroepiandrosterone, etc);Systemic radionuclides (eg, samarium or strontium);Vaccine therapy; Hypoglycemic episode requiring medical intervention while on insulin treatment within 12 months before day 1; Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide<br>160 mg administered as four 40 mg soft gelatin capsules orally once daily | Drug: Enzalutamide<br>* 160 mg administered as four soft gelatin capsules orally once daily<br>* Other names: MDV3100;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population | Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of complete response (CR), partial response(PR), stable disease(SD) for >= 16 weeks on radiologic imaging based on Investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1(RECIST 1.1). An estimate of the percentage and its exact 2-sided 85% confidence interval(CI) were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10mm short axis. PR: At least 30% decrease in sum of longest diameter (LD) of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference | Week 16 | 
| Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population | Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of CR, PR, or SD for >= 16 weeks on radiologic imaging based on Investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population | Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 24 | 
| Percentage of Participants With Clinical Benefit at Week 24: ITT Population | Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. | Week 24 | 
| Percentage of Participants With Best Objective Response: Evaluable Population | Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | 
| Percentage of Participants With Best Objective Response: ITT Population | Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | 
| Progression-Free Survival (PFS): Evaluable Population | PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | 
| Progression-Free Survival: ITT Population | PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | From Baseline up to disease progression or death due to any cause (up to 87 Weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, triple negative, androgen receptor positive