Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer
- Conditions
- Advanced, Androgen Receptor Positive Triple Negative Breast Cancer
- Interventions
- 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
- 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.
- 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
Texas Oncology - Memorial City
🇺🇸Houston, Texas, United States
Florida Cancer Specialist South Division
🇺🇸Fort Myers, Florida, 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
Northwestern Medical Faculty Foundation(NMFF)/ Women's Cancer Center Shared Laboratories
🇺🇸Chicago, Illinois, United States
Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center, Investigational Drug Service Department of Pharmacy
🇺🇸Chicago, Illinois, United States
The University of Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States
Indiana University Health Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Investigational Drug Services
🇺🇸Indianapolis, Indiana, United States
Sidney and Lois Eskenazi Hospital
🇺🇸Indianapolis, Indiana, United States
Springmill Medical Clinic
🇺🇸Indianapolis, Indiana, United States
Oncology Hematology Care, Inc.
🇺🇸Fairfield, Ohio, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The West Clinic, PC
🇺🇸Memphis, Tennessee, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University Infusion Center Pharmacy
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-West County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center
🇺🇸Saint Peters, Missouri, United States
Hematology Oncology Associates of Northern NJ
🇺🇸Morristown, New Jersey, United States
Memorial Sloan Kettering - I Chemotherapy Practice/Investigational Drug Service
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Wesley Long Community Hospital
🇺🇸Greensboro, North Carolina, United States
Greenville Health System
🇺🇸Spartanburg, South Carolina, United States
Tennessee Oncology, PLLC
🇺🇸Smyrna, Tennessee, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Vanderbilt Breast Center at One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
Vanderbilt Health Pharmacy One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology - Longview Cancer Center
🇺🇸Longview, Texas, United States
Texas Oncology-Tyler
🇺🇸Tyler, Texas, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Virginia Oncology Associates
🇺🇸Virginia Beach, Virginia, United States
Institut Jules Bordet
🇧🇪Brussels, Belgium
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre-Cedars Cancer Centre
🇨🇦Montreal, Quebec, Canada
Department of Radiology
🇬🇧Truro, England, United Kingdom
Pharmacy Department
🇬🇧Truro, England, United Kingdom
3rd Floor,Oncology Link office
🇮🇪Dublin, Ireland
Institute for Cancer Research
🇮🇪Dublin, Ireland
Mater Private Hospital
🇮🇪Dublin, Ireland
Radiology Department
🇬🇧Nottingham, England, United Kingdom
U.O Farmaceutica, Nuovo Ospedale di Prato Palazzina dei servizi
🇮🇹Prato, Italy
Hospital Universitario HM Monteprincipe
🇪🇸Boadilla del Monte, Madrid, Spain
Grupo Hospitalario Quiron - Hospital Quiron Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 Octubre
🇪🇸Madrid, Spain
Centro Intergral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital de Madrid Norte-Sanchinarro.
🇪🇸Madrid, Spain
Clinical Investigation and Research Unit
🇬🇧Brighton, England, United Kingdom
Radiation Safety Service, Medical Physics Department
🇬🇧Brighton, England, United Kingdom
Histopathology Department
🇬🇧Nottingham, England, United Kingdom
Nottingham University Hospital
🇬🇧Nottingham, England, United Kingdom
Royal Cornwall Hospitals NHS trust
🇬🇧Truro, Cornwall, England, United Kingdom