NCT01946204

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men with high-risk non-metastatic castration-resistant prostate cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,207

participants targeted

Target at P75+ for phase_3

Timeline
20mo left

Started Oct 2013

Longer than P75 for phase_3

Geographic Reach
24 countries

375 active sites

Status
active not recruiting

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

Study Progress88%
Oct 2013Dec 2027

First Submitted

Initial submission to the registry

September 17, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 19, 2013

Completed
25 days until next milestone

Study Start

First participant enrolled

October 14, 2013

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 19, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

June 19, 2018

Completed
9.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Expected
Last Updated

April 13, 2026

Status Verified

April 1, 2026

Enrollment Period

3.6 years

First QC Date

September 17, 2013

Results QC Date

May 18, 2018

Last Update Submit

April 9, 2026

Conditions

Keywords

Prostate neoplasmsProstate cancerCastration-resistant prostate cancerNon-metastatic castration-resistant prostate cancerARN-509Apalutamide

Outcome Measures

Primary Outcomes (1)

  • Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)

    MFS was defined as the time from randomization to the time of first evidence of BICR-confirmed bone or soft tissue distant metastasis or death due to any cause, whichever occurred first. The MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and computerized tomography \[CT\] or magnetic resonance imaging \[MRI\] of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.

    Up to approximately 43 Months

Secondary Outcomes (5)

  • Time to Metastasis (TTM)

    Up to approximately 43 Months

  • Progression-free Survival (PFS)

    Up to approximately 43 Months

  • Time to Symptomatic Progression

    Up to approximately 43 Months

  • Overall Survival

    Up to approximately 43 months

  • Time to Initiation of Cytotoxic Chemotherapy

    Up to approximately 43 months

Study Arms (2)

Treatment Arm A: Apalutamide

EXPERIMENTAL
Drug: Apalutamide

Treatment Arm B: Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

240 mg tablets administered by mouth on a continuous once daily dosing regimen

Treatment Arm A: Apalutamide

Matched placebo tablets administered by mouth on a continuous once daily dosing regimen

Treatment Arm B: Placebo

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equal to (\<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous ADT (androgen deprivation therapy)
  • Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (\>) 2 nanogram per milliliter (ng/mL)
  • Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study
  • Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization
  • Patients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout
  • At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors, estrogens, and any other anti-cancer therapy prior to randomization
  • At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
  • Eastern Cooperative Oncology Group Performance Status 0 or 1
  • Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade \<= 1 or baseline prior to randomization
  • Adequate organ function according to protocol-defined criteria
  • Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility

You may not qualify if:

  • Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement
  • Symptomatic local or regional disease requiring medical intervention
  • Prior treatment with second generation anti-androgens
  • Prior treatment with CYP17 inhibitors
  • Prior treatment with radiopharmaceutical agents, or any other investigational agent for non-metastatic castration-resistant prostate cancer
  • Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting
  • History of seizure or condition that may pre-dispose to seizure
  • Concurrent therapy with protocol-defined excluded medications
  • History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months prior to randomization; uncontrolled hypertension; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (379)

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Chandler, Arizona, United States

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Tucson, Arizona, United States

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Duarte, California, United States

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Fullerton, California, United States

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Laguna Woods, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Bernardino, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Sherman Oaks, California, United States

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Stanford, California, United States

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Tarzana, California, United States

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Torrance, California, United States

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Denver, Colorado, United States

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Englewood, Colorado, United States

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Glenwood Springs, Colorado, United States

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Grand Junction, Colorado, United States

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Washington D.C., District of Columbia, United States

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Aventura, Florida, United States

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Boca Raton, Florida, United States

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Bradenton, Florida, United States

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Daytona Beach, Florida, United States

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Fort Myers, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Orlando, Florida, United States

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Sarasota, Florida, United States

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St. Petersburg, Florida, United States

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Wellington, Florida, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Decatur, Illinois, United States

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Maywood, Illinois, United States

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Melrose Park, Illinois, United States

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Carmel, Indiana, United States

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Jeffersonville, Indiana, United States

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Muncie, Indiana, United States

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West Des Moines, Iowa, United States

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Westwood, Kansas, United States

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Wichita, Kansas, United States

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Metairie, Louisiana, United States

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New Orleans, Louisiana, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Rockville, Maryland, United States

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Towson, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Lansing, Michigan, United States

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Minneapolis, Michigan, United States

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Royal Oak, Michigan, United States

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Duluth, Minnesota, United States

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Bay Saint Louis, Mississippi, United States

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Southaven, Mississippi, United States

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Kansas City, Missouri, United States

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Missoula, Montana, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Hooksett, New Hampshire, United States

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Hackensack, New Jersey, United States

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Lawrenceville, New Jersey, United States

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Morristown, New Jersey, United States

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Mount Laurel, New Jersey, United States

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New Brunswick, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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Oneida, New York, United States

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Poughkeepsie, New York, United States

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Syracuse, New York, United States

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The Bronx, New York, United States

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Concord, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Salisbury, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Middleburg Heights, Ohio, United States

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Middletown, Ohio, United States

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Bend, Oregon, United States

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Portland, Oregon, United States

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Tualatin, Oregon, United States

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Bala-Cynwyd, Pennsylvania, United States

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Bryn Mawr, Pennsylvania, United States

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Lancaster, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Warwick, Rhode Island, United States

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Charleston, South Carolina, United States

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Greenville, South Carolina, United States

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Myrtle Beach, South Carolina, United States

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West Columbia, South Carolina, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Abilene, Texas, United States

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Amarillo, Texas, United States

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Dallas, Texas, United States

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Fort Sam Houston, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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San Antonio, Texas, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Burien, Washington, United States

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Edmonds, Washington, United States

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Seattle, Washington, United States

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Tacoma, Washington, United States

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Green Bay, Wisconsin, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Adelaide, Australia

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Box Hill, Australia

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Camperdown, Australia

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Darlinghurst, Australia

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Geelong, Australia

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Gosford, Australia

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Hobart, Australia

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Kogarah, Australia

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Liverpool, Australia

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Melbourne, Australia

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Nedlands, Australia

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Parkville, Australia

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South Woodville, Australia

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Southport, Australia

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Sydney, Australia

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Tweed Heads, Australia

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Wollongong, Australia

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Graz, Austria

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Innsbruck, Austria

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Linz, Austria

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Vienna, Austria

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Brussels, Belgium

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Ghent, Belgium

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Kortrijk, Belgium

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Leuven, Belgium

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Liège, Belgium

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Ottignies, Belgium

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Abbotsford British Columbia, British Columbia, Canada

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Kelowna, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Moncton, New Brunswick, Canada

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Saint John, New Brunswick, Canada

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Halifax, Nova Scotia, Canada

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Barrie, Ontario, Canada

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Brampton, Ontario, Canada

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Brantford, Ontario, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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North York, Ontario, Canada

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Oakville, Ontario, Canada

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Ottawa, Ontario, Canada

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Owen Sound, Ontario, Canada

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Toronto, Ontario, Canada

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Gatineau, Quebec, Canada

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Granby, Quebec, Canada

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Greenfield Park, Quebec, Canada

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Laval, Quebec, Canada

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Montreal, Quebec, Canada

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Pointe-Claire, Quebec, Canada

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Liberec, Czechia

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Olomouc, Czechia

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Opava, Czechia

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Pilsen, Czechia

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Prague, Czechia

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Aalborg C, Denmark

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Copenhagen, Denmark

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Odense, Denmark

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Roskilde, Denmark

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Helsinki, Finland

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Oulu, Finland

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Seinäjoki, Finland

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Tampere, Finland

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Turku, Finland

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Angers, France

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Besançon, France

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Bordeaux, France

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Caen Cédex 05, France

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Clermont-Ferrand, France

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Hyers, France

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La Roche-sur-Yon, France

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Le Mans, France

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Lille Cedex N/a, France

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Lyon, France

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Marseille, France

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Nice, France

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Nîmes, France

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Paris, France

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Reims, France

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Rennes, France

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Rouen, France

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Saint-Grégoire, France

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Saint-Herblain, France

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Strasbourg, France

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Suresnes, France

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Tours, France

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Vandœuvre-lès-Nancy, France

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Aachen, Germany

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Bergisch Gladbach, Germany

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Berlin, Germany

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Braunschweig, Germany

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Cologne, Germany

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Duisburg, Germany

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Emmendingen, Germany

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Frankfurt am Main, Germany

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Göttingen, Germany

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Greifswald, Germany

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Hamburg, Germany

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Hanover, Germany

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Heidelberg, Germany

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Heinsberg, Germany

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Homburg/Saar, Germany

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Jena, Germany

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Kiel, Germany

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Kirchheim unter Teck, Germany

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Magdeburg, Germany

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Mainz, Germany

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Mannheim, Germany

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Marburg, Germany

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Mettmann, Germany

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Müllheim, Germany

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Münster, Germany

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Nürtingen, Germany

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Regensburg, Germany

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Rostock, Germany

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Tübingen, Germany

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Weiden, Germany

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Wilhelmshaven, Germany

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Wuppertan, Germany

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Zirndorf, Germany

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Budapest, Hungary

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Miskolc, Hungary

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Nyíregyhá, Hungary

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Sopron, Hungary

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Szentes, Hungary

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Haifa, Israel

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Jeruselem, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Tel Aviv, Israel

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Ẕerifin, Israel

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Akita, Japan

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Fukuoka, Japan

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Gifu, Japan

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Hakodate, Japan

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Hiroshima, Japan

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Hokkaido, Japan

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Kanazawa, Japan

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Kashiwa, Japan

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Kita-Gun, Japan

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Kobe, Japan

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Koshigaya, Japan

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Kumamoto, Japan

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Kurume, Japan

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Matsuyama, Japan

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Nagano, Japan

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Nagasaki, Japan

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Nagoya, Japan

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Niigata, Japan

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Osaka, Japan

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Ōsaka-sayama, Japan

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Sagamihara, Japan

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Sakura, Japan

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Sapporo, Japan

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Shinjuku-Ku, Japan

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Tokushima, Japan

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Tokyo, Japan

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Ube, Japan

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Wakayama, Japan

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Yokohama, Japan

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Alkmaar, Netherlands

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Eindhoven, Netherlands

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Hoofddorp, Netherlands

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Leidschendam, Netherlands

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Auckland, New Zealand

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Christchurch, New Zealand

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Hamilton, New Zealand

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Nelson, New Zealand

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Tauranga, New Zealand

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Whangarei, New Zealand

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Nordbyhagen, Norway

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Bialystok, Poland

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Bydgoszcz, Poland

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Gdansk, Poland

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Kutno, Poland

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Lodz, Poland

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Poznan, Poland

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Szczecin, Poland

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Torun, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Baia Mare, Romania

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Brasov, Romania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Târgu Mureş, Romania

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Barnaul, Russia

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Ivanovo, Russia

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Moscow, Russia

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Obninsk, Russia

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Omsk, Russia

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Ryazan, Russia

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Saint Petersburg, Russia

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Ufa, Russia

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Yaroslavl, Russia

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Yekaterinburg, Russia

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Banská Bystrica, Slovakia

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Bratislava, Slovakia

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Martin, Slovakia

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Nitra, Slovakia

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Trenčín, Slovakia

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Daegu, South Korea

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Gwangju, South Korea

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Pusan, South Korea

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Seongnam, South Korea

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Seoul, South Korea

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A Coruña, Spain

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Badalona, Spain

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Barcelona, Spain

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Castellon, Spain

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Girona, Spain

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Guadalajara, Spain

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Jerez de la Frontera, Spain

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Las Palmas de Gran Canaria, Spain

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Madrid, Spain

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Málaga, Spain

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Murcia, Spain

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Palma de Mallorca, Spain

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Pamplona, Spain

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Sabadell, Spain

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Salamanca, Spain

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San Sebastián de los Reyes, Spain

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Santander, Spain

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Seville, Spain

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Valencia, Spain

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Gothenburg, Sweden

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Örebro, Sweden

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Stockholm, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Kaohsiung City, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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Taoyuan, Taiwan

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Blackburn, United Kingdom

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Cambridge, United Kingdom

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Cardiff, United Kingdom

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Dundee, United Kingdom

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Glasgow, United Kingdom

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Guildford, United Kingdom

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Leeds, United Kingdom

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London, United Kingdom

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Maidstone, United Kingdom

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Metropolitan Borough of Wirral, United Kingdom

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Nottingham, United Kingdom

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Plymouth, United Kingdom

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Southampton, United Kingdom

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Surrey, United Kingdom

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Swansea, United Kingdom

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Wolverhampton, United Kingdom

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Related Publications (11)

  • Ni X, Sui J, Wang B, Wang H, Freedland SJ, Ye D, Zhu Y. Lower Testosterone Level and Metastases-Free Survival in Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With Novel Antiandrogens: A Post Hoc Analysis of SPARTAN and ARAMIS. J Urol. 2025 Jul;214(1):10-17. doi: 10.1097/JU.0000000000004545. Epub 2025 Mar 25.

  • Feng FY, Smith MR, Saad F, Mobadersany P, Tian SK, Yip SSF, Greshock J, Khan N, Yu MK, McCarthy S, Brookman-May SD, Bourla AB, Todorovic T, Yamashita R, Huang HC, Royce TJ, Showalter TN, Griffin J, Mitani A, Esteva A, Small EJ. Digital Pathology-Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer. JCO Precis Oncol. 2025 Jan;9:e2400653. doi: 10.1200/PO-24-00653. Epub 2025 Jan 31.

  • Roy S, Malone S, Wing K, Chowdhury S, Kishan AU, Sun Y, Wallis CJD, Mohamad O, Jia AY, Swami U, Zaorsky NG, Morgan SC, Ong M, Agarwal N, Spratt DE, Small EJ, Saad F. Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of the SPARTAN Randomized Clinical Trial. JAMA Netw Open. 2024 Oct 1;7(10):e2439434. doi: 10.1001/jamanetworkopen.2024.39434.

  • Karsh LI, Bevans KB, Saad F, Chung BH, Oudard S, Brookman-May SD, McCarthy SA, Smith MR, Chi KN, Small EJ, Agarwal N. Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies. Future Oncol. 2024;20(35):2689-2698. doi: 10.1080/14796694.2024.2384257. Epub 2024 Aug 20.

  • Shen J, Chowdhury S, Agarwal N, Karsh LI, Oudard S, Gartrell BA, Feyerabend S, Saad F, Pieczonka CM, Chi KN, Brookman-May SD, Rooney B, Bhaumik A, McCarthy SA, Bevans KB, Mundle SD, Small EJ, Smith MR, Graff JN. Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024 Jan;130(1):73-81. doi: 10.1038/s41416-023-02492-8. Epub 2023 Nov 11.

  • Pollock Y, Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik B, Olmos D, Lee JY, Uemura H, Bhaumik A, Londhe A, Rooney B, Brookman-May SD, De Porre P, Mundle SD, Small EJ. Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide. Prostate Cancer Prostatic Dis. 2023 Mar;26(1):156-161. doi: 10.1038/s41391-022-00592-9. Epub 2022 Oct 8.

  • Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, Van Sanden S, Diels J, Hadaschik BA. Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison. Adv Ther. 2022 Jan;39(1):518-531. doi: 10.1007/s12325-021-01885-6. Epub 2021 Nov 19.

  • Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.

  • Smith MR, Mehra M, Nair S, Lawson J, Small EJ. Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2020 Apr;18(2):e180-e189. doi: 10.1016/j.clgc.2019.10.030. Epub 2019 Nov 6.

  • Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. doi: 10.1016/S1470-2045(18)30456-X. Epub 2018 Sep 10.

  • Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Limitations and Caveats

These results are up to clinical cutoff (CCO) date (that is, 19 May 2017).

Results Point of Contact

Title
Senior Medical Director, WC Clinical Oncology Department
Organization
Janssen Research & Development, LLC

Study Officials

  • Aragon Pharmaceuticals, Inc. Clinical Trial

    Aragon Pharmaceuticals, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 17, 2013

First Posted

September 19, 2013

Study Start

October 14, 2013

Primary Completion

May 19, 2017

Study Completion (Estimated)

December 31, 2027

Last Updated

April 13, 2026

Results First Posted

June 19, 2018

Record last verified: 2026-04

Locations