A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT01212991
First received: September 29, 2010
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to determine the benefit of enzalutamide versus placebo as assessed by overall survival and progression-free survival in patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy but not yet received chemotherapy.


Condition Intervention Phase
Prostate Cancer
Drug: Enzalutamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy

Resource links provided by NLM:


Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization to death due to any cause. For patients who were alive at the time of the analysis data cutoff, overall survival was censored at the last date the patient was known to be alive or analysis data cutoff date, whichever was first. This included patients who were known to have died after the data analysis cutoff date. Patients with no post-baseline survival information were censored on the date of randomization.

  • Radiographic Progression-free Survival [ Time Frame: During study period (up to 20 months) ] [ Designated as safety issue: No ]
    Radiographic progression-free survival was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause within 168 days after treatment discontinuation, whichever was first. Radiographic disease progression was evaluated by CT scan or MRI and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using RECIST 1.1 for soft tissue disease and PCWG2 guidelines for bone disease. Patients who did not reach the endpoint were censored at their last assessment.


Secondary Outcome Measures:
  • Time to First Skeletal-related Event [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    Time to first skeletal-related event was defined as the time from randomization to the date of the first occurrence of a skeletal-related event for each patient. A skeletal-related event was defined as radiation therapy or surgery to bone for prostate cancer, pathological bone fracture, spinal cord compression, or initiation/change in antineoplastic therapy to treat bone pain from prostate cancer. Skeletal-related events were recorded at each scheduled and unscheduled study visit and during long-term follow-up if a skeletal-related event was not documented previously. Patients who did not have a skeletal-related event at the time of the analysis data cutoff were censored at the date of last assessment indicating no evidence of skeletal-related event. Patients with no postbaseline assessments were censored on the date of randomization.

  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    The time to initiation of cytotoxic chemotherapy is defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for the treatment of prostate cancer for each patient. For patients who did not start cytotoxic chemotherapy at the time of the analysis data cutoff, time to initiation of cytotoxic chemotherapy was censored at the date of last assessment where no cytotoxic chemotherapy was indicated or at the analysis data cutoff date, whichever was first. Time to initiation of cytotoxic chemotherapy for patients with no postbaseline assessments was censored on the date of randomization.

  • Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    Time to PSA progression was defined as the time from randomization to date of first confirmed observation of PSA progression for each patient. For patients with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, and confirmed 3 or more weeks later. For patients with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above baseline was documented, and confirmed 3 or more weeks later. For patients who did not have confirmed PSA progression at the time of the analysis data cutoff, time to PSA progression was censored at the date of the last PSA assessment showing no evidence of confirmed PSA progression or the analysis data cutoff date, whichever was first. Time to PSA progression for patients with no postbaseline assessments was censored on the date of randomization.

  • Percentage of Patients With Prostate Specific Antigen (PSA) Response ≥ 50% [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    PSA response was defined as a ≥ 50% reduction in PSA from baseline to the lowest postbaseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later. Patients were evaluable for PSA response rate if a patient had a PSA level measured at baseline and at least one postbaseline assessment.

  • Best Overall Soft Tissue Response [ Time Frame: During study period (up to 3 years) ] [ Designated as safety issue: No ]
    The best overall soft tissue objective response is defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only patients with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of participants with measurable soft tissue disease at screening in each treatment group.


Enrollment: 1717
Study Start Date: September 2010
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide Drug: Enzalutamide
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.
Placebo Comparator: Placebo Drug: Placebo
Participants received placebo, administered as four capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Randomized, Double Blind Treatment Period:

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
  • Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony disease
  • No prior treatment with cytotoxic chemotherapy
  • Asymptomatic or mildly symptomatic from prostate cancer

Exclusion Criteria:

  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
  • Known or suspected brain metastasis or active leptomeningeal disease
  • History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer

Open-Label Treatment Period:

The following inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment.

Eligible patients must meet all inclusion criteria.

  • Received randomized double-blind treatment in PREVAIL;
  • Open-label day 1 visit is within 6 months after this amendment is approved and becomes effective at the study site;
  • Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy;

The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must not meet any of the following criteria:

  • Has taken commercially available enzalutamide (Xtandi);
  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
  • Known or suspected brain metastasis or active leptomeningeal disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01212991

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Beverly Hills, California, United States, 90211
Los Angeles, California, United States, 90024
Los Angeles, California, United States, 90033
Sacramento, California, United States, 95817
San Diego, California, United States, 92123
Stanford, California, United States, 94305
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Boca Raton, Florida, United States, 33486
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Kentucky
Louisville, Kentucky, United States, 40245
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 2115
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Omaha, Nebraska, United States, 68114
United States, Nevada
Las Vegas, Nevada, United States, 89135
United States, New York
New York, New York, United States, 11201
New York, New York, United States, 10029
United States, North Carolina
Cary, North Carolina, United States, 27518
Charlotte, North Carolina, United States, 28211
Durham, North Carolina, United States, 27710
Raleigh, North Carolina, United States, 27607
United States, Oregon
Portland, Oregon, United States, 97239
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Dallas, Texas, United States, 75235
United States, Virginia
Newport News, Virginia, United States, 23502
Norfolk, Virginia, United States, 23502
Virginia Beach, Virginia, United States, 23456
United States, Washington
Seattle, Washington, United States, 98109
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Australia, New South Wales
Concord, New South Wales, Australia
Hornsby, New South Wales, Australia, 2077
Kogarah, New South Wales, Australia
Lismore, New South Wales, Australia
Liverpool, New South Wales, Australia
Port Macquarie, New South Wales, Australia
Randwick, New South Wales, Australia
St. Leonards, New South Wales, Australia, 2065
Tamworth, New South Wales, Australia, 2340
Wahroonga, New South Wales, Australia
Waratah, New South Wales, Australia
Westmead, New South Wales, Australia
Australia, Queensland
Herston, Queensland, Australia
South Brisbane, Queensland, Australia
Australia, South Australia
Kurralta Park, South Australia, Australia
Australia, Victoria
Bendigo, Victoria, Australia
Box Hill, Victoria, Australia
East Bentleigh, Victoria, Australia, 3144
East Melbourne, Victoria, Australia
Footscray, Victoria, Australia
Geelong, Victoria, Australia
Heidelberg, Victoria, Australia
Malvern, Victoria, Australia, 3144
Parkville, Victoria, Australia
Australia
New South Wales, Australia
Austria
Wien, Vienna, Austria
Graz, Austria
Linz, Austria
Salzburg, Austria, 5020
Salzburg, Austria
Wien, Austria
Belgium
Bruxelles, Belgium
Gent, Belgium
Hasselt, Belgium
Kortrijk, Belgium
Leuven, Belgium
Liege, Belgium
Roeselare, Belgium
Canada, Alberta
Calgary, Alberta, Canada
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Kelowna, British Columbia, Canada, V1Y 5L3
Vancouver, British Columbia, Canada, V5Z 1M9
Victoria, British Columbia, Canada
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Nova Scotia
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton, Ontario, Canada
London, Ontario, Canada
Ottawa, Ontario, Canada
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H2L 4M
Quebec City, Quebec, Canada, G1R 3S3
Sherbrooke, Quebec, Canada
Denmark
Aalborg, Denmark
Aarhus, Denmark
Copenhagen, Denmark
Frederiksberg, Denmark
Herlev, Denmark
Roskilde, Denmark
Finland
Helsinki, Finland
Oulu, Finland
Tampere, Finland
France
Angers, France
Avignon, France
Bordeaux, France
Bordeaux, France, 33075
La Roche sur Yon, France
Le Mans, France
Lyon, France
Paris, France
Paris, France, 75475
Paris, France, 75005
Paris, France, 75230
Paris Cedex 15, France
Rennes, France
Saint Herblain, France
Saint Priest en Jarez, France
Strasbourg, France
Toulouse, France
Villejuif, France
Germany
Berlin, Germany, 12203
Braunschweig, Germany
Dresden, Germany
Hamburg, Germany, 20246
Hamburg, Germany, 22399
Hannover, Germany, 98109
Heidelberg, Germany
Homburg, Germany, 66421
Mannheim, Germany
Munster, Germany, 48149
Tubingen, Germany, 72076
Ulm, Germany
Weiden, Germany, 92637
Israel
Beer-Sheva, Israel
Haifa, Israel
Petah Tiqva, Israel
Ramat Gan, Israel
Zerifin, Israel
Italy
Arezzo, Italy
Cremona, Italy
Meldola, Italy
Orbassano, Italy, 10043
Ravenna, Italy, 5-48121
Rimini, Italy
Roma, Italy
Japan
Chiba, Japan
Fukuoka, Japan, 812-0033
Fukuoka, Japan, 812-8582
Hokkaido, Japan, 060-8543
Kanagawa, Japan
Kyoto, Japan, 6068507
Kyoto, Japan
Miyagi, Japan, 980-8574
Nagasaki, Japan, 8528501
Niigata, Japan
Osaka, Japan, 5458586
Osaka, Japan, 5378511
Osaka, Japan, 565-0871
Osaka, Japan
Shizuoka, Japan, 4313192
Tokushima, Japan, 7708503
Tokyo, Japan, 142-8666
Tokyo, Japan
Tokyo, Japan, 181-8619
Tokyo, Japan, 1358550
Tokyo, Japan, 160-8582
Tokyo, Japan, 113-8603
Yamagata, Japan
Yamaguchi, Japan, 755-8505
Korea, Republic of
Gyenoggi-do, Korea, Republic of, 410-769
Gyeonggi-do, Korea, Republic of, 410-769
Jeonnam, Korea, Republic of
Seoul, Korea, Republic of, 135-720
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 138-736
Seoul, Korea, Republic of, 137-701
Lithuania
Klaipeda, Lithuania
Vilnius, Lithuania
Netherlands
Amsterdam, Netherlands
Eindhoven, Netherlands, 5623 EJ
Groningen, Netherlands
RB Groningen, Netherlands, 9713 GZ
Poland
Gdansk, Poland, 80-211
Lodz, Poland, 93-509
Myslowice, Poland
Poznan, Poland
Wroclaw, Poland
Wroclaw, Poland, 54-144
Russian Federation
Moscow, Russian Federation
St. Petersburg, Russian Federation
St. Petersburg, Russian Federation, 197022
Singapore
Singapore, Singapore
Singapore, Singapore, 119074
Slovakia
Banska Bystrica, Slovakia
Bratislava, Slovakia
Martin, Slovakia
Nitra, Slovakia
Presov, Slovakia
Spain
Barcelona, Cataluna, Spain
Sabadell, Cataluna, Spain
Pamplona, Navarra, Spain
Badalona, Spain
Barcelona, Spain, 08036
Barcelona, Spain
La Coruna, Spain
Madrid, Spain, 28034
Madrid, Spain
Manresa, Spain
Palma de Mallorca, Spain
Sweden
Goteborg, Sweden
Malmo, Sweden
Orebro, Sweden
Stockholm, Sweden
Umea, Sweden
United Kingdom
Brighton, United Kingdom
Bristol, United Kingdom
Cardiff, United Kingdom
Edinburgh, United Kingdom
London, United Kingdom
London, United Kingdom, W12 0NN
London, United Kingdom, SE1 9RT
Merseyside, United Kingdom
Newcastle upon Tyne, United Kingdom
Northwood, United Kingdom
Oxford, United Kingdom
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Medivation, Inc.
Astellas Pharma Inc
  More Information

No publications provided by Medivation, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medivation, Inc.
ClinicalTrials.gov Identifier: NCT01212991     History of Changes
Other Study ID Numbers: MDV3100-03
Study First Received: September 29, 2010
Results First Received: October 8, 2014
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Medivation, Inc.:
Progressive Metastatic Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 29, 2014