A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

NCT ID: NCT01288911

Last Updated: 2024-12-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

375 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-22

Study Completion Date

2017-11-08

Brief Summary

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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.

Detailed Description

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An open-label period was added to the main protocol. Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over bicalutamide as assessed by the primary endpoint, all ongoing enzalutamide treated participants and ongoing or previous bicalutamide treated participants that met entry criteria were offered open-label enzalutamide at the discretion of the participant and study investigators.

Conditions

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Prostatic Neoplasms

Keywords

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Metastatic MDV3100 Prostate progressive Cancer enzalutamide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Enzalutamide

Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.

Group Type EXPERIMENTAL

enzalutamide

Intervention Type DRUG

capsules

Bicalutamide

Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.

Group Type ACTIVE_COMPARATOR

bicalutamide

Intervention Type DRUG

tablets

Interventions

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enzalutamide

capsules

Intervention Type DRUG

bicalutamide

tablets

Intervention Type DRUG

Other Intervention Names

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MDV3100 Casodex

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Condom (barrier method of contraception), AND
2. In addition to a condom, one of the following acceptable forms of contraception is required:

* Established use of oral, injected or implanted hormonal methods of contraception.
* Placement of an intrauterine device (IUD) or intrauterine system (IUS).
* Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
* Tubal ligation for at least 6 months prior to Screening
* Vasectomy or other surgical castration at least 6 months prior to Screening

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

Carolina Urologic Research Center

Associate Medical Science Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development

Locations

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Site US1934

Homewood, Alabama, United States

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Site US1527

Anchorage, Alaska, United States

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Site US3026

Tucson, Arizona, United States

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Site US2977

Highland, California, United States

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Site US3630

San Diego, California, United States

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Site US2935

Denver, Colorado, United States

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Site US2945

Middlebury, Connecticut, United States

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Site US2014

Melrose Park, Illinois, United States

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Site US2067

Springfield, Illinois, United States

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Site US2027

Jeffersonville, Indiana, United States

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Site US1838

West Des Moines, Iowa, United States

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Site US62

Kansas City, Kansas, United States

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Site US2976

Baltimore, Maryland, United States

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Site US3182

Bethesda, Maryland, United States

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Site US2975

Ann Arbor, Michigan, United States

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Site US892

Grand Rapids, Michigan, United States

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Site US20

Minneapolis, Minnesota, United States

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Site US3078

Billings, Montana, United States

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Site US2968

Lawrenceville, New Jersey, United States

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Site US3025

Poughkeepsie, New York, United States

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Site US1675

Rochester, New York, United States

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Site US2934

Staten Island, New York, United States

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Site US81

Chapel Hill, North Carolina, United States

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Site US2104

Greensboro, North Carolina, United States

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Site US44

Cincinnati, Ohio, United States

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Site US2185

Columbus, Ohio, United States

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Site US1598

Bala-Cynwyd, Pennsylvania, United States

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Site US1680

Lancaster, Pennsylvania, United States

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Site US2926

Myrtle Beach, South Carolina, United States

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Site US1657

Nashville, Tennessee, United States

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Site US464

Houston, Texas, United States

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Site US2978

San Antonio, Texas, United States

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Site US1653

Virginia Beach, Virginia, United States

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Site US1580

Burien, Washington, United States

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Site US1709

Wenatchee, Washington, United States

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Site US51

Milwaukee, Wisconsin, United States

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Site BE3015

Brussels, , Belgium

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Site BE1322

Ghent, , Belgium

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Site BE3018

Kortrijk, , Belgium

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Site BE3288

Leuven, , Belgium

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Site BE3289

Liège, , Belgium

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Site BE3013

Turnhout, , Belgium

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Site CA3104

Calgary, Alberta, Canada

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Site CA3242

Abbotsford, British Columbia, Canada

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Site CA2646

Kingston, Ontario, Canada

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Site CA166

Toronto, Ontario, Canada

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Site CA3084

Toronto, Ontario, Canada

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Site CA2984

Granby, Quebec, Canada

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Site CA170

Montreal, Quebec, Canada

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Site DK3354

Aalborg, , Denmark

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Site DK3356

Aarhus, , Denmark

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Site DK1857

Copenhagen, , Denmark

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Site DK1263

Herlev, , Denmark

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Site FR1091

Créteil, , France

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Site FR3009

Lille, , France

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Site FR442

Lyon, , France

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Site FR3002

Paris, , France

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Site FR3003

Poitiers, , France

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Site FR3000

Rennes, , France

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Site FR3007

Rouen, , France

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Site FR3005

Suresnes, , France

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Site DE4000

Nürtingen, Baden-Wurttemberg, Germany

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Site DE2989

Aachen, , Germany

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Site DE3287

Bergisch Gladbach, , Germany

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Site DE2993

Bonn, , Germany

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Site DE2995

Bonn, , Germany

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Site DE2994

Bonn, , Germany

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Site DE2990

Hamburg, , Germany

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Site DE3270

Hanover, , Germany

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Site DE2992

Reutlingen, , Germany

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Site DE3286

Waldshut-Tiengen, , Germany

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Site DE2988

Wuppertal, , Germany

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Site RO3042

Bucharest, RO, Romania

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Site RO3039

Bucharest, RO, Romania

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Site RO3035

Bucharest, , Romania

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Site GB3029

Bristol, UK, United Kingdom

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Site GB3027

London, UK, United Kingdom

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Site GB3030

London, UK, United Kingdom

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Site GB3028

Cardiff, Wales, United Kingdom

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Site GB3244

Belfast, , United Kingdom

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Site GB2702

Cambridge, , United Kingdom

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Site GB3166

Glasgow, , United Kingdom

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Site GB1862

Leicher, , United Kingdom

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Site GB3163

London, , United Kingdom

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Site GB2624

Manchester, , United Kingdom

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Site GB3355

Merseyside, , United Kingdom

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Site GB3245

Northwood, Middlesex, , United Kingdom

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Site GB3290

Preston, , United Kingdom

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Countries

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United States Belgium Canada Denmark France Germany Romania United Kingdom

References

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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.

Reference Type DERIVED
PMID: 30189902 (View on PubMed)

Heidenreich 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.

Reference Type DERIVED
PMID: 27497762 (View on PubMed)

Shore 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.

Reference Type DERIVED
PMID: 26774508 (View on PubMed)

Related Links

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https://astellasclinicalstudyresults.com/study.aspx?ID=282

Link to results on the Astellas Clinical Study Results website

Other Identifiers

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2010-021868-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

9785-CL-0222

Identifier Type: -

Identifier Source: org_study_id