Efficacy and Safety Study of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: exemestane; Drug: exemestane; Drug: Placebo (for enzalutamide)

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.

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZA
    • Wilrijk, Antwerpen, Belgium, 2610
      • GZA
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center- Cedars Cancer Center
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Cedars Cancer Centre
• Ireland
  • Dublin, Ireland, 4
    • St Vincent's University Hospital
  • Dublin, Ireland, 7
    • Mater Private Hospital
  • Dublin, Ireland, 4
    • Pharmacy Department
  • Dublin, Ireland, 4
    • Radiology Department
  • Dublin, Ireland, 7
    • Institute for Cancer Research
  • Dublin, Ireland, 7
    • Pharmacy Department
  • Dublin, Ireland, 7
    • Radiology Department
  • Dublin, Ireland, D9
    • Cancer Clinical Trials Unit
  • Dublin, Ireland, D9
    • Pharmacy Department
  • Dublin, Ireland, D9
    • Radiology Department
  • Dublin, Ireland
    • Pharmacy Department
  • Dublin, Ireland
    • Radiology Department
  • Dublin 7, Ireland
    • Mater Private Hospital
  • Dublin 7, Ireland
    • Institute for Cancer Research
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliera S.Orsola Malpighi
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Prato, Italy, 59100
    • U.O. Farmaceutica, Nuovo Ospedale di Prato
  • Prato, Italy, 59100
    • U.O. Oncologia Medica, Nuovo Ospedale di Prato
  • Roma, Italy, 00144
    • Dipartimento di Oncologia Medica, Istituto Nazionale Tumori Regina Elena
  • MI
    • Milano, MI, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • Milano, MI, Italy, 20141
      • Divisione di Senologia Medica; Istituto Europeo di Oncologia
  • PG
    • Perugia, PG, Italy, 06132
      • A.O.di Perugia S. Maria Della Misericoridia
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08028
    • Grupo Hospitalario Quiron - Hospital Universitari Quiron Dexeus
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre
  • Madrid, Spain, 28050
    • Centro Integral Oncológico Clara Campal
  • Madrid, Spain, 28050
    • Hospital de Madrid Norte Sanchinarro
  • Madrid
    • Boadilla del Monte, Madrid, Spain, 28660
      • Hospital Universitario HM Monteprincipe
• United Kingdom
  • England
    • Brighton, England, United Kingdom, BN2 5BE
      • Brighton and Sussex University Hospital NHS Trust
    • Brighton, England, United Kingdom, BN2 5BE
      • Pharmacy Department
    • Brighton, England, United Kingdom, BN2 5BE
      • Radiation Safety Service, Medical Physics Department
    • Nottingham, England, United Kingdom, NG5 1PB
      • Histopathology Department
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham University Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Pharmacy Department
    • Nottingham, England, United Kingdom, NG5 1PB
      • Radiology Department
    • Nottingham, England, United Kingdom, NG7 2UH
      • Radiology Department
    • Truro, England, United Kingdom, TR1 3LJ
      • Department of Radiology
    • Truro, England, United Kingdom, TR1 3LJ
      • Pharmacy Department
    • Truro, England, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospitals NHS Trust
  • Sussex
    • Brighton, Sussex, United Kingdom, BN2 5BE
      • Clinical Investigation & Research Unit
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora, Colorado, United States, 80045
      • ATTN-Research Pharmacist
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital, Anschutz Outpatient Pavilion
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Cancer Specialists
    • Bonita Springs, Florida, United States, 34135
      • Florida Cancer Specialists
    • Bradenton, Florida, United States, 34209
      • Florida Cancer Specialists
    • Brandon, Florida, United States, 33511
      • Florida Cancer Specialists
    • Cape Coral, Florida, United States, 33914
      • Florida Cancer Specialists
    • Cape Coral, Florida, United States, 33909
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33761
      • Florida Cancer Specialists
    • Englewood, Florida, United States, 34223
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33905
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33908
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists
    • Hudson, Florida, United States, 34667
      • Florida Cancer Specialists
    • Largo, Florida, United States, 33770
      • Florida Cancer Specialists
    • Naples, Florida, United States, 34102
      • Florida Cancer Specialists
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Specialists
    • Orange City, Florida, United States, 32763
      • Florida Cancer Specialists
    • Orlando, Florida, United States, 32806
      • Florida Cancer Specialists
    • Port Charlotte, Florida, United States, 33980
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34236
      • Florida Cancer Specialists
    • Spring Hill, Florida, United States, 34608
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists
    • Tavares, Florida, United States, 32778
      • Florida Cancer Specialists
    • Venice, Florida, United States, 34285
      • Florida Cancer Specialists
    • Venice, Florida, United States, 34292
      • Florida Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center,
    • New Lenox, Illinois, United States, 60451
      • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Hospital
    • Indianapolis, Indiana, United States, 46290
      • Springmill Medical Clinic
    • Indianapolis, Indiana, United States, 46202
      • Investigational Drug Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System DBA Virginia Piper Cancer Institute
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A
    • Minneapolis, Minnesota, United States, 55407
      • Dr.Michaela Tsai
  • Mississippi
    • Corinth, Mississippi, United States, 38834
      • The West Clinic, P.C.
    • Southaven, Mississippi, United States, 38671
      • The West Clinic, P.C. d/b/a West Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Barnes-jewish Hospital
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63110
      • Washington University Infusion Center Pharmacy
    • Saint Louis, Missouri, United States, 63141
      • Siteman Cancer Center- West County
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Hematology Oncology Associates of Northern NJ
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care, Inc.
    • Cincinnati, Ohio, United States, 45211
      • Oncology Hematology Care, Inc.
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care, Inc.
    • Cincinnati, Ohio, United States, 45202
      • Oncology Hematology Care, Inc.
    • Fairfield, Ohio, United States, 45014
      • Oncology Hematology Care, Inc.
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic, P.C. d/b/a West Cancer Center
    • Memphis, Tennessee, United States, 38104
      • The West Clinic, P.C. d/b/a West Cancer Center
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Breast Center at One Hundred Oaks
    • Nashville, Tennessee, United States, 37211
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Health Pharmacy One Hundred Oaks
  • Texas
    • Fort Worth, Texas, United States, 76177
      • Investigational Products Center (IPC)
    • Fort Worth, Texas, United States, 76177
      • Investigational Products Center(IPC)
    • Fort Worth, Texas, United States, 76177
      • Investigational Products center
    • Fort Worth, Texas, United States, 76177
      • lnvestigational Products Center (IPC)
    • Houston, Texas, United States, 77024
      • Texas Oncology - Memorial City
    • Longview, Texas, United States, 75601
      • Texas Oncology-Longview Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Mechanicsville, Virginia, United States, 23116-1844
      • Virginia Cancer Institute
    • Midlothian, Virginia, United States, 23114
      • Virginia Cancer Institute
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
    • Richmond, Virginia, United States, 23235-4730
      • Virginia Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enzalutamide & exemestane; Enzalutamide 160 mg/day administered as four 40mg soft gelatin capsules by mouth once daily with or without food and exemestane 50mg (two 25mg tablets overencapsulated as a single capsule during the blinded portion of the study and two 25mg tablets after unblinding) once daily after food.	Drug: Enzalutamide; 160 mg/day administered as four 40mg soft gelatin capsules by mouth once daily with or without food.; Other Names: MDV3100; XTANDI; Drug: exemestane; 25mg (overencapsulated to match 50mg dose during the blinded portion of the study and one 25mg tablet after unblinding) by mouth once daily after food.; Other Names: Aromasin; Drug: exemestane; 50mg (two 25mg tablets overencapsulated as a single capsule during the blinded portion of the study and two 25mg tablets after unblinding) by mouth once daily after food.; Other Names: Aromasin
Active Comparator: Placebo & exemestane; Placebo and exemestane 25mg (overencapsulated to match 50mg dose during the blinded portion of the study and one 25mg tablet without placebo after unblinding) once daily after food.	Drug: exemestane; 25mg (overencapsulated to match 50mg dose during the blinded portion of the study and one 25mg tablet after unblinding) by mouth once daily after food.; Other Names: Aromasin; Drug: exemestane; 50mg (two 25mg tablets overencapsulated as a single capsule during the blinded portion of the study and two 25mg tablets after unblinding) by mouth once daily after food.; Other Names: Aromasin; Drug: Placebo (for enzalutamide); Sugar pill manufactured to mimic enzalutamide administered as four soft gelatin capsules by mouth once daily with or without food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS): Intent-to-Treat (ITT) Population By Interactive Web Recognition System (IWRS)	PFS was defined as the time in months from randomization to the first documentation of progression of disease (PD) or death on study due to any cause, whichever occurred first. PD according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) was defined as greater than or equal to (>=) 20 percent (%) increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.	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)
Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS)	PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1, was defined as >= 20% increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate-24 (CBR-24)	CBR-24: Percentage of participants with a best response of complete response (CR), partial response (PR), or stable disease (SD) sustained for atleast 24 weeks, as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during study as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions.	From randomization up to 3 years
Best Objective Response Rate	Best objective response rate: Percentage of participants with measurable disease and with a best response of CR or PR according to RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: Atleast 30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. Response evaluation was based on investigators' judgment.	From randomization until CR or PR, whichever occurred first (up to 3 years)
Duration of Objective Response	Duration of objective response: Time from first documentation of CR or PR, to the first documentation of PD or death due to any cause, whichever occurred first as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants with no PD or death (after initial CR or PR) at the analysis date were censored at last tumor assessment date prior to date of new antitumor treatment or data cutoff.	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)
Time to Response	Time to response: Time from randomization to first documentation of CR or PR. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who were not known to have had a CR or PR were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.	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)
Time to Progression	Time to progression was defined as the time from the date of randomization to PD defined by the investigator using RECIST 1.1. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who did not experience disease progression, time to progression was right censored at the date of the last tumor assessment prior to data cutoff or date of new antitumor treatment, whichever occurred first.	From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years)
Progression Free Survival (PFS) at 6 Months	PFS at 6 months was defined as the percentage of participants with no event of disease progression at Month 6 landmark, estimated by Kaplan-Meier methods. PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. The analysis of PFS was based on investigator assessment of disease progression.	Month 6
Concentration Versus Time Summary of Enzalutamide	Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.	Predose on Day 29, 57 and 113
Concentration Versus Time Summary of Exemestane	Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.	Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169
Concentration Versus Time Summary of N-desmethyl Enzalutamide	N-desmethyl enzalutamide was the active metabolite of enzalutamide. Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.	Predose on Day 29, 57 and 113

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core Questionnaire (QLQ-C30)		Month 24
European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Module (QLQ-BR23)		Month 24
Number of Participants With Positive Androgen Receptor (AR) Expression by Immunohistochemistry (IHC)		Day 1, 29, 57, 113 and 169
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.	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)
Number of Participants With Treatment-Emergent Adverse Events of Grade 3 or Higher Severity	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only the participants with treatment-emergent AEs of grade 3 (severe) or higher grade were reported in this outcome measure.	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)
Number of Participants With Clinically Significant Vital Sign Abnormalities	Criteria for clinically significant vital sign abnormalities: Systolic blood pressure (SBP): absolute SBP <90 millimeters of mercury (mmHg) and decrease from baseline (DFB) >30 mmHg, absolute SBP>180 mmHg and increase from baseline (IFB) >40 mmHg, final visit or 2 consecutive visits SBP >=20 mmHg change from baseline (CFB), most extreme post-baseline SBP >=140 mmHg, most extreme post-baseline SBP >=180 mmHg, most extreme SBP >=140 mmHg and >=20 mmHg CFB, most extreme SBP >=180 mmHg and >=20 mmHg CFB; diastolic blood pressure (DBP): absolute DBP > 105 mmHg and IFB >30 mmHg, absolute DBP <50 mmHg and DFB >20 mmHg, final visit or 2 consecutive visits DBP >=15 mmHg CFB, most extreme post-baseline DBP >=90 mmHg, most extreme post-baseline DBP >=105 mmHg, most extreme DBP >=90 mmHg and >=15 mmHg CFB, most extreme DBP >=105 mmHg and >=15 mmHg CFB; heart rate <50 beats per minute (BPM) and DFB >20 BPM or heart rate >120 BPM and IFB >30 BPM.	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)
Number of Participants With Clinically Significant Laboratory Abnormalities	Laboratory tests included hematology (hematocrit, hemoglobin, platelet count, red blood cell count, total neutrophils [absolute] and white blood cell count with differential) and serum chemistry (albumin, alkaline phosphatase, alanine aminotransferase [ALT], aspartate transaminase [AST], blood urea nitrogen and creatinine, calcium, sodium, potassium, chloride, glucose (non-fasting), lactate dehydrogenase, magnesium, phosphorus/phosphate, total bilirubin, total bicarbonate, total protein and uric acid). Clinically significant abnormality evaluation was based on clinical investigator's judgment.	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)
Progression Free Survival (PFS): By Electronic Data Capture (EDC)	PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1 was defined >=20 % increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first. Cht 1: Enz + Exe = Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg; Cht 2: Enz + Exe= Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg	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)
Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Electronic Data Capture (EDC)	PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1, was defined as >= 20% increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.	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)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Astellas Pharma Inc; Medivation, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2013
• Primary Completion (Actual): September 23, 2016
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 5, 2013
• First Posted (Estimate): December 10, 2013

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: MDV3100; enzalutamide; advanced breast cancer; Estrogen receptor positive (ER +); Progesterone receptor positive (PgR +); HER-2 normal
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: MDV3100-12; 2013-002717-35 (EudraCT Number); C3431008 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.