Clinical trial NCT02007512: Efficacy and Safety Study of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer
Official title: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF EFFICACY AND SAFETY OF ENZALUTAMIDE IN COMBINATION WITH EXEMESTANE IN PATIENTS WITH ADVANCED BREAST CANCER THAT IS ESTROGEN OR PROGESTERONE RECEPTOR-POSITIVE AND HER2-NORMAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: advanced breast cancer
enzalutamide
MDV3100
Estrogen receptor positive (ER +)
Progesterone receptor positive (PgR +)
HER-2 normal
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation, Inc.
First posted: 2013-12-10
Enrollment: 247
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if enzalutamide given in combination with exemestane is safe and effective in patients with advanced breast cancer.

Detailed description: This is a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Efficacy and Safety of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer That Is Estrogen or Progesterone Receptor Positive and HER2-Normal.

Eligibility criteria: Inclusion Criteria:

* Willing and able to provide informed consent;
* Postmenopausal;
* Advanced histologically confirmed breast cancer that is ER+, PgR+, or both, and HER-2 normal;
* Up to one prior hormone therapy and up to one prior chemotherapy in the advanced setting is allowed;
* Availability of a representative, formalin-fixed, paraffin-embedded tumor specimen that enabled the diagnosis of breast cancer with viable tumor cells in a tissue block or unstained serial slides accompanied bay an associated pathology report;
* Measurable disease. Patients with non-measurable bone or skin disease as their only manifestation of advanced breast cancer are also eligible;
* Eastern Cooperative Oncology Group (ECOG) status of 0 or 1;

Exclusion Criteria:

* Any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator;
* 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, in the opinion of the investigator;
* Current or previously treated brain metastasis or leptomeningeal disease;
* Prior therapy (\> 28 days) with exemestane in the metastatic setting (Patients receiving exemestane in the adjuvant setting and having disease recurrence more than 1 year after treatment discontinuation are eligible);
* Requires treatment for tuberculosis or HIV infection;
* Radiation therapy within 7 days before randomization;
* History of another invasive cancer within 5 years before randomization;
* History of seizure or any condition that may predispose to seizure;
* Clinically significant cardiovascular disease;
* Active gastrointestinal disorder;
* Major surgery within 28 days prior to randomization;
* Treatment with any oral anticancer or with any non-hormonal anticancer agent within 14 days before randomization;
* Treatment with any approved or investigational agent that blocks androgen synthesis or targets the androgen receptor;
* Treatments with any of the following medications within 14 days before randomization: Estrogens, Androgens, or Systemic radionuclides;
* Hypersensitivity reaction to exemestane.

Primary outcomes:
measure: Progression Free Survival (PFS): Intent-to-Treat (ITT) Population By Interactive Web Recognition System (IWRS)
timeFrame: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
measure: Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS)
timeFrame: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Secondary outcomes:
measure: Clinical Benefit Rate-24 (CBR-24)
timeFrame: From randomization up to 3 years
measure: Best Objective Response Rate
timeFrame: From randomization until CR or PR, whichever occurred first (up to 3 years)
measure: Duration of Objective Response
timeFrame: From first documentation of CR or PR until PD, or last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
measure: Time to Response
timeFrame: From randomization until first documentation of CR or PR, or last tumor assessment without PD or death prior to new antitumor treatment initiation, whichever occurred first (up to 3 years)
measure: Time to Progression
timeFrame: From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years)
measure: Progression Free Survival (PFS) at 6 Months
timeFrame: Month 6
measure: Concentration Versus Time Summary of Enzalutamide
timeFrame: Predose on Day 29, 57 and 113
measure: Concentration Versus Time Summary of Exemestane
timeFrame: Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169
measure: Concentration Versus Time Summary of N-desmethyl Enzalutamide
timeFrame: Predose on Day 29, 57 and 113
Other outcomes:
measure: European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core Questionnaire (QLQ-C30)
timeFrame: Month 24
measure: European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Module (QLQ-BR23)
timeFrame: Month 24
measure: Number of Participants With Positive Androgen Receptor (AR) Expression by Immunohistochemistry (IHC)
timeFrame: Day 1, 29, 57, 113 and 169
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
measure: Number of Participants With Treatment-Emergent Adverse Events of Grade 3 or Higher Severity
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
measure: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
measure: Progression Free Survival (PFS): By Electronic Data Capture (EDC)
timeFrame: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
measure: Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Electronic Data Capture (EDC)
timeFrame: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Locations:
city: Aurora
country: United States
facility: ATTN-Research Pharmacist
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital, Anschutz Outpatient Pavilion
state: Colorado
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 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: Cape Coral
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Clearwater
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Englewood
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 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
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,
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: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health System DBA Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Dr.Michaela Tsai
state: Minnesota
city: Corinth
country: United States
facility: The West Clinic, P.C.
state: Mississippi
city: Southaven
country: United States
facility: The West Clinic, P.C. d/b/a West Cancer Center
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 Cancer Center
state: New York
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: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Germantown
country: United States
facility: The West Clinic, P.C. d/b/a West Cancer Center
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: Memphis
country: United States
facility: The West Clinic, P.C. d/b/a West Cancer Center
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: Henry-Joyce Cancer Clinic
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Fort Worth
country: United States
facility: Investigational Products Center (IPC)
state: Texas
city: Fort Worth
country: United States
facility: Investigational Products Center(IPC)
state: Texas
city: Fort Worth
country: United States
facility: Investigational Products center
state: Texas
city: Fort Worth
country: United States
facility: lnvestigational Products Center (IPC)
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: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Edegem
country: Belgium
facility: UZA
state: Antwerpen
city: Wilrijk
country: Belgium
facility: GZA
state: Antwerpen
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center- Cedars Cancer Center
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre - Cedars Cancer Centre
state: Quebec
city: Dublin 7
country: Ireland
facility: Institute for Cancer Research
city: Dublin 7
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: Pharmacy Department
city: Dublin
country: Ireland
facility: Radiology Department
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
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: Dublin
country: Ireland
facility: Cancer Clinical Trials Unit
city: Dublin
country: Ireland
facility: Pharmacy Department
city: Dublin
country: Ireland
facility: Radiology Department
city: Dublin
country: Ireland
facility: Pharmacy Department
city: Dublin
country: Ireland
facility: Radiology Department
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: MI
city: Milano
country: Italy
facility: Divisione di Senologia Medica; Istituto Europeo di Oncologia
state: MI
city: Perugia
country: Italy
facility: A.O.di Perugia S. Maria Della Misericoridia
state: PG
city: Bologna
country: Italy
facility: Azienda Ospedaliera S.Orsola Malpighi
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Prato
country: Italy
facility: U.O. Farmaceutica, Nuovo Ospedale di Prato
city: Prato
country: Italy
facility: U.O. Oncologia Medica, Nuovo Ospedale di Prato
city: Roma
country: Italy
facility: Dipartimento di Oncologia Medica, Istituto Nazionale Tumori Regina Elena
city: Boadilla del Monte
country: Spain
facility: Hospital Universitario HM Monteprincipe
state: Madrid
city: Barcelona
country: Spain
facility: Grupo Hospitalario Quiron - Hospital Universitari Quiron Dexeus
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 Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital de Madrid Norte Sanchinarro
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospital NHS Trust
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
country: United Kingdom
facility: Department of Radiology
state: England
city: Truro
country: United Kingdom
facility: Pharmacy Department
state: England
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS trust
state: England
city: Brighton
country: United Kingdom
facility: Clinical Investigation & Research Unit
state: Sussex
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: