A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
2 other identifiers
interventional
375
8 countries
88
Brief Summary
The purpose of this study was to determine the efficacy and safety of oral enzalutamide compared to bicalutamide in castrate men with metastatic prostate cancer who have progressed while on Luteinizing Hormone Receptor Hormone (LHRH) agonist/antagonist or after receiving a bilateral orchiectomy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2011
Longer than P75 for phase_2
88 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2011
CompletedFirst Posted
Study publicly available on registry
February 3, 2011
CompletedStudy Start
First participant enrolled
March 22, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 19, 2014
CompletedResults Posted
Study results publicly available
December 3, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
November 8, 2017
CompletedDecember 6, 2024
November 1, 2024
3.6 years
February 1, 2011
October 15, 2015
November 19, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.
From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
Secondary Outcomes (11)
PFS Based on Investigator Assessment
From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
Prostate-specific Antigen (PSA) Response by Week 13
Baseline to Week 13
Best PSA Response
Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
Time to PSA Progression
From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
Time to PSA ≤ 4 ng/mL
From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
- +6 more secondary outcomes
Study Arms (2)
Enzalutamide
EXPERIMENTALParticipants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Bicalutamide
ACTIVE COMPARATORParticipants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of randomization or bilateral orchiectomy (i.e., surgical or medical castration)
- Metastatic disease documented by one of the following:
- At least two bone lesions on bone scan, or
- Soft tissue disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI), or
- Unequivocal pelvic adenopathy short axis \> 2.0 cm in diameter by CT/MRI
- Progressive disease at study entry defined as one or more of the following three criteria occurring in the setting of castrate levels of testosterone:
- Prostate Specific Antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value should be ≥ 2 µg/L (2 ng/mL);
- Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
- Bone disease progression defined by two or more new lesions on bone scan
- Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 must be \< 4); no use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to randomization
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including subjects with decreased performance status not attributed to progressive and symptomatic prostate cancer
- Estimated life expectancy of ≥ 12 months
- Able to swallow the study drug and comply with study requirements
- A male subject and his female spouse/partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period, and for 3 months after final study drug administration. Two acceptable forms of birth control include:
- +7 more criteria
You may not qualify if:
- Prior cytotoxic chemotherapy for prostate cancer
- Severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment
- Known or suspected brain and/or skull metastasis or active epidural disease
- History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
- Current or prior treatment with estrogens and/or drugs with anti-androgenic properties such as spironolactone \> 50 mg/day, or progestational agents for the treatment of prostate cancer within 6 months prior to randomization
- Current or prior use of ketoconazole for the treatment of prostate cancer
- Use of antiandrogens within 6 weeks prior to randomization
- Documented prior disease progression while receiving antiandrogens. Disease progression defined as PSA progression, radiographic progression and/or clinical deterioration.
- Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within 6 months prior to randomization
- Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3 months prior to randomization or expectation of their use during the study
- Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to randomization
- Major surgery within 2 months prior to randomization
- History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization
- Clinically significant cardiovascular disease including myocardial infarction within past six months or uncontrolled angina within past three months
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (88)
Site US1934
Homewood, Alabama, 35209, United States
Site US1527
Anchorage, Alaska, 99503, United States
Site US3026
Tucson, Arizona, 85715, United States
Site US2977
Highland, California, 92346, United States
Site US3630
San Diego, California, 92123, United States
Site US2935
Denver, Colorado, 80211, United States
Site US2945
Middlebury, Connecticut, 06762, United States
Site US2014
Melrose Park, Illinois, 60160, United States
Site US2067
Springfield, Illinois, 62703, United States
Site US2027
Jeffersonville, Indiana, 47130, United States
Site US1838
West Des Moines, Iowa, 50266, United States
Site US62
Kansas City, Kansas, 66160-7233, United States
Site US2976
Baltimore, Maryland, 21201, United States
Site US3182
Bethesda, Maryland, 20889-5600, United States
Site US2975
Ann Arbor, Michigan, 48109, United States
Site US892
Grand Rapids, Michigan, 49546, United States
Site US20
Minneapolis, Minnesota, 55455, United States
Site US3078
Billings, Montana, 59101, United States
Site US2968
Lawrenceville, New Jersey, 08648, United States
Site US3025
Poughkeepsie, New York, 12601, United States
Site US1675
Rochester, New York, 14642, United States
Site US2934
Staten Island, New York, 10304, United States
Site US81
Chapel Hill, North Carolina, 27599, United States
Site US2104
Greensboro, North Carolina, 27403, United States
Site US44
Cincinnati, Ohio, 45267, United States
Site US2185
Columbus, Ohio, 43221, United States
Site US1598
Bala-Cynwyd, Pennsylvania, 19004, United States
Site US1680
Lancaster, Pennsylvania, 17604, United States
Site US2926
Myrtle Beach, South Carolina, 29572, United States
Site US1657
Nashville, Tennessee, 37209, United States
Site US464
Houston, Texas, 77030, United States
Site US2978
San Antonio, Texas, 78229, United States
Site US1653
Virginia Beach, Virginia, 23462, United States
Site US1580
Burien, Washington, 98166, United States
Site US1709
Wenatchee, Washington, 98801, United States
Site US51
Milwaukee, Wisconsin, 53226, United States
Site BE3015
Brussels, 1090, Belgium
Site BE1322
Ghent, 9000, Belgium
Site BE3018
Kortrijk, 8500, Belgium
Site BE3288
Leuven, 3000, Belgium
Site BE3289
Liège, Belgium
Site BE3013
Turnhout, 2300, Belgium
Site CA3104
Calgary, Alberta, T2V 1P9, Canada
Site CA3242
Abbotsford, British Columbia, V2S 3N5, Canada
Site CA2646
Kingston, Ontario, K7L 2V7, Canada
Site CA166
Toronto, Ontario, M4N 3M5, Canada
Site CA3084
Toronto, Ontario, M5G 2M9, Canada
Site CA2984
Granby, Quebec, J2G 8Z9, Canada
Site CA170
Montreal, Quebec, H3G 1A4, Canada
Site DK3354
Aalborg, 9000, Denmark
Site DK3356
Aarhus, 8200, Denmark
Site DK1857
Copenhagen, 2200, Denmark
Site DK1263
Herlev, 2730, Denmark
Site FR1091
Créteil, 94010, France
Site FR3009
Lille, 59037, France
Site FR442
Lyon, 69437, France
Site FR3002
Paris, 75020, France
Site FR3003
Poitiers, 86000, France
Site FR3000
Rennes, 35033, France
Site FR3007
Rouen, 76031, France
Site FR3005
Suresnes, 92151, France
Site DE4000
Nürtingen, Baden-Wurttemberg, 72622, Germany
Site DE2989
Aachen, 51074, Germany
Site DE3287
Bergisch Gladbach, D-51465, Germany
Site DE2993
Bonn, 53105, Germany
Site DE2995
Bonn, 53111, Germany
Site DE2994
Bonn, 53117, Germany
Site DE2990
Hamburg, 22081, Germany
Site DE3270
Hanover, 30625, Germany
Site DE2992
Reutlingen, 72764, Germany
Site DE3286
Waldshut-Tiengen, 29761, Germany
Site DE2988
Wuppertal, 42103, Germany
Site RO3042
Bucharest, RO, 022328, Romania
Site RO3039
Bucharest, RO, 050659, Romania
Site RO3035
Bucharest, 041345, Romania
Site GB3029
Bristol, UK, BS2 8HW, United Kingdom
Site GB3027
London, UK, SE19RT, United Kingdom
Site GB3030
London, UK, SW17 0QT, United Kingdom
Site GB3028
Cardiff, Wales, CF14 4XW, United Kingdom
Site GB3244
Belfast, BT9 7AB, United Kingdom
Site GB2702
Cambridge, CB2 0QQ, United Kingdom
Site GB3166
Glasgow, G12 0YN, United Kingdom
Site GB1862
Leicher, LE5 4PW, United Kingdom
Site GB3163
London, NW1 2PG, United Kingdom
Site GB2624
Manchester, M20 4BX, United Kingdom
Site GB3355
Merseyside, CH63 4JY, United Kingdom
Site GB3245
Northwood, Middlesex, HA6 2RN, United Kingdom
Site GB3290
Preston, PR2 9HT, United Kingdom
Related Publications (3)
Schultz NM, Shore ND, Chowdhury S, Klotz LH, Concepcion RS, Penson DF, Karsh LI, Yang H, Brown BA, Barlev A, Flanders SC. Number-needed-to-treat analysis of clinical progression in patients with metastatic castration-resistant prostate cancer in the STRIVE and TERRAIN trials. BMC Urol. 2018 Sep 6;18(1):77. doi: 10.1186/s12894-018-0387-7.
PMID: 30189902DERIVEDHeidenreich A, Chowdhury S, Klotz L, Siemens DR, Villers A, Ivanescu C, Holmstrom S, Baron B, Wang F, Lin P, Shore ND. Impact of Enzalutamide Compared with Bicalutamide on Quality of Life in Men with Metastatic Castration-resistant Prostate Cancer: Additional Analyses from the TERRAIN Randomised Clinical Trial. Eur Urol. 2017 Apr;71(4):534-542. doi: 10.1016/j.eururo.2016.07.027. Epub 2016 Aug 3.
PMID: 27497762DERIVEDShore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. doi: 10.1016/S1470-2045(15)00518-5. Epub 2016 Jan 14.
PMID: 26774508DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Executive Medical Director
- Organization
- Astellas Pharma Global Development, Inc. (APGD)
Study Officials
- PRINCIPAL INVESTIGATOR
Principal Investigator
Carolina Urologic Research Center
- STUDY DIRECTOR
Associate Medical Science Director
Astellas Pharma Global Development
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2011
First Posted
February 3, 2011
Study Start
March 22, 2011
Primary Completion
October 19, 2014
Study Completion
November 8, 2017
Last Updated
December 6, 2024
Results First Posted
December 3, 2015
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will not share
Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.