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

Phase 2

Completed

Conditions: Advanced, Androgen Receptor Positive Triple Negative Breast Cancer

Interventions: Drug: Enzalutamide

Registration Number: NCT01889238

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 118

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Enzalutamide	Enzalutamide	160 mg administered as four 40 mg soft gelatin capsules orally once daily

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population	Week 16	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.
Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population	Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population	Week 24	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.
Percentage of Participants With Clinical Benefit at Week 24: ITT Population	Week 24	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.
Percentage of Participants With Best Objective Response: Evaluable Population	From Baseline up to disease progression or death due to any cause (up to 87 Weeks)	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.
Percentage of Participants With Best Objective Response: ITT Population	From Baseline up to disease progression or death due to any cause (up to 87 Weeks)	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.
Progression-Free Survival (PFS): Evaluable Population	From Baseline up to disease progression or death due to any cause (up to 87 Weeks)	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.
Progression-Free Survival: ITT Population	From Baseline up to disease progression or death due to any cause (up to 87 Weeks)	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.
Time to Response: Evaluable Population	From first dose of study drug until first documentation of CR or PR or data censoring date, whichever occurred first (up to 87 Weeks)	The time to response is defined as the time from the date of first dose of study drug to initial CR or PR. Participants without response of CR or PR before the data cutoff date were censored at the last tumor assessment date before the data cutoff. Kaplan-Meier method was used to summarize time to response.
Duration of Response: Evaluable Population	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (up to 87 Weeks)	Duration of objective response is defined as the time from initial CR or PR to documented disease progression or death due to any cause, whichever occurs first. Participants without disease progression or death due to any cause before the data cutoff date were censored at the last tumor assessment date before the data cutoff.
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4	From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)	Laboratory parameters included hematology parameters \[low lymphocytes (10\^6/L), neutrophils (10\^6/L) and Leukocytes (10\^9/L)\] and chemistry parameters \[high phosphate (mmol/L), bilirubin, Alkaline phosphatase (U/L) and glucose (mmol/L)\]. Number of participants with postbaseline laboratory toxicity Grade 3 or 4 as per NCI-CTCAE (version 4.0) (Grade 3= Severe, Grade 4= Life-threatening) were reported.

Trial Locations

Locations (70): Rocky Mountain Cancer Center Sky Ridge
🇺🇸
Lone Tree, Colorado, United States
Florida Cancer Specialist South Division
🇺🇸
Fort Myers, Florida, United States
Texas Oncology - Memorial City
🇺🇸
Houston, Texas, United States
UZA
🇧🇪
Edegem, Antwerpen, Belgium
Cancer Clinical Trials Unit, Mid-Western Cancer center
🇮🇪
Limerick, Ireland
Dipartimento di Oncologia Medica, IRCCS Ospedale San Raffaele
🇮🇹
Milano, Italy
Farmacia (magazzino ricevimento merc), IRCCS Ospedale San Raffaele
🇮🇹
Milano, Italy
U.O. Oncologia Medica, Nuovo Ospedale di Prato
🇮🇹
Prato, Italy
Rocky Mountain Cancer Centers
🇺🇸
Lone Tree, Colorado, United States
Florida Cancer Specialists
🇺🇸
Venice, Florida, United States
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Rocky Mountain Cancer Center Sky Ridge
🇺🇸Lone Tree, Colorado, United States