Clinical trial NCT01889238: Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced, Androgen Receptor Positive Triple Negative Breast Cancer
Keywords: breast cancer
triple negative
androgen receptor positive
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2013-06-28
Enrollment: 118
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population
timeFrame: Week 16
measure: Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population
timeFrame: Week 24
measure: Percentage of Participants With Clinical Benefit at Week 24: ITT Population
timeFrame: Week 24
measure: Percentage of Participants With Best Objective Response: Evaluable Population
timeFrame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
measure: Percentage of Participants With Best Objective Response: ITT Population
timeFrame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
measure: Progression-Free Survival (PFS): Evaluable Population
timeFrame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
measure: Progression-Free Survival: ITT Population
timeFrame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
measure: Time to Response: Evaluable Population
timeFrame: From first dose of study drug until first documentation of CR or PR or data censoring date, whichever occurred first (up to 87 Weeks)
measure: Duration of Response: Evaluable Population
timeFrame: 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)
measure: Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4
timeFrame: 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)
Other outcomes:
measure: Trough Plasma Concentration of Enzalutamide and Its Metabolite
timeFrame: Predose on Day 1 (Baseline), Week 9 and Week 17
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 87 weeks
measure: Number of Participants With Study Drug Discontinuation Due to Adverse Events
timeFrame: Baseline up to 87 weeks
measure: Number of Participants With Grade 3 or Higher Adverse Events
timeFrame: Baseline up to 87 weeks
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: 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)
measure: Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades
timeFrame: 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)
Locations:
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Center Sky Ridge
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Altamonte Springs
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Bonita Springs
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Bradenton
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Brandon
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Cape Coral
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Clearwater
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialist South Division
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Hudson
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Largo
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Naples
country: United States
facility: Florida Cancer Specialists
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orange City
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Port Charlotte
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Spring Hill
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tavares
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation(NMFF)/ Women's Cancer Center Shared Laboratories
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center, Investigational Drug Service Department of Pharmacy
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Drug Services
state: Indiana
city: Indianapolis
country: United States
facility: Sidney and Lois Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Springmill Medical Clinic
state: Indiana
city: Crestview Hills
country: United States
facility: Oncology Hematology Care, Inc.
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Corinth
country: United States
facility: The West Clinic, PC
state: Mississippi
city: Southaven
country: United States
facility: The West Clinic, PC
state: Mississippi
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Infusion Center Pharmacy
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-West County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Morristown
country: United States
facility: Hematology Oncology Associates of Northern NJ
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering - I Chemotherapy Practice/Investigational Drug Service
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Greensboro
country: United States
facility: Wesley Long Community Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Fairfield
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System
state: South Carolina
city: Spartanburg
country: United States
facility: Greenville Health System
state: South Carolina
city: Dickson
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic, PC
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic, PC
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Breast Center at One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Health Pharmacy One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Mechanicsville
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Midlothian
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Edegem
country: Belgium
facility: UZA
state: Antwerpen
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre-Cedars Cancer Centre
state: Quebec
city: Dooradoyle
country: Ireland
facility: Department of Radiology
state: Limerick
city: Dublin 4
country: Ireland
facility: Pharmacy Department
city: Dublin
country: Ireland
facility: 3rd Floor,Oncology Link office
city: Dublin
country: Ireland
facility: Department of Radiology
city: Dublin
country: Ireland
facility: Institute for Cancer Research
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: Pharmacy Department
city: Dublin
country: Ireland
facility: Radiology Department
city: Limerick
country: Ireland
facility: Cancer Clinical Trials Unit, Mid-Western Cancer center
city: Limerick
country: Ireland
facility: Pharmacy Department
city: Milano
country: Italy
facility: Dipartimento di Oncologia Medica, IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Farmacia (magazzino ricevimento merc), IRCCS Ospedale San Raffaele
city: Prato
country: Italy
facility: U.O Farmaceutica, Nuovo Ospedale di Prato Palazzina dei servizi
city: Prato
country: Italy
facility: U.O. Oncologia Medica, Nuovo Ospedale di Prato
city: Boadilla del Monte
country: Spain
facility: Hospital Universitario HM Monteprincipe
state: Madrid
city: Barcelona
country: Spain
facility: Grupo Hospitalario Quiron - Hospital Quiron Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
city: Madrid
country: Spain
facility: Centro Intergral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital de Madrid Norte-Sanchinarro.
city: Brighton
country: United Kingdom
facility: Clinical Investigation and Research Unit
state: England
city: Brighton
country: United Kingdom
facility: Pharmacy Department
state: England
city: Brighton
country: United Kingdom
facility: Radiation Safety Service, Medical Physics Department
state: England
city: Nottingham
country: United Kingdom
facility: Histopathology Department
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Pharmacy Department
state: England
city: Nottingham
country: United Kingdom
facility: Radiology Department
state: England
city: Nottingham
country: United Kingdom
facility: Radiology Department
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospitals NHS trust
state: England
city: Truro
country: United Kingdom
facility: Department of Radiology
state: England
city: Truro
country: United Kingdom
facility: Pharmacy Department
state: England
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_CHAIR
References:
citation: Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. J Clin Oncol. 2018 Mar 20;36(9):884-890. doi: 10.1200/JCO.2016.71.3495. Epub 2018 Jan 26.
citation: Kumar V, Yu J, Phan V, Tudor IC, Peterson A, Uppal H. Androgen Receptor Immunohistochemistry as a Companion Diagnostic Approach to Predict Clinical Response to Enzalutamide in Triple-Negative Breast Cancer. JCO Precis Oncol. 2017 Nov;1:1-19. doi: 10.1200/PO.17.00075.