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A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC (TITAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02489318
Recruitment Status : Active, not recruiting
First Posted : July 3, 2015
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE July 1, 2015
First Posted Date  ICMJE July 3, 2015
Last Update Posted Date February 7, 2020
Actual Study Start Date  ICMJE November 27, 2015
Estimated Primary Completion Date November 4, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2016)
  • Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to 54 Months ]
    The rPFS is defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to 54 Months ]
    The OS is defined as the time from date of randomization to date of death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: July 1, 2015)
  • Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to 76 Months ]
    The rPFS is defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to 76 Months ]
    The OS is defined as the time from date of randomization to date of death from any cause.
Change History Complete list of historical versions of study NCT02489318 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • Time to Pain Progression [ Time Frame: Up to 54 Months ]
    Time to pain progression is defined as the time from the date of randomization to the date of the first observation of pain progression.
  • Time to Skeletal-Related Event (SRE) [ Time Frame: Up to 54 Months ]
    Time to SRE is defined as the time from the date of randomization to the date of the first occurrence of a fracture or treatment for the fracture. The SRE is defined as the occurrence of symptomatic pathological fracture, spinal cord compression, radiation to new bone lesions, or surgery to bone.
  • Time to Chronic Opioid Use [ Time Frame: Up to 54 Months ]
    Time to chronic opioid use is defined as the time from date of randomization to the first date of opioid use or first date of an increase in the total daily dose.
  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to 54 Months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2015)
  • Time to Pain Progression [ Time Frame: Up to 76 Months ]
    Time to pain progression is defined as the time from the date of randomization to the date of the first observation of pain progression.
  • Time to Skeletal-Related Event (SRE) [ Time Frame: Up to 76 Months ]
    Time to SRE is defined as the time from the date of randomization to the date of the first occurrence of a fracture or treatment for the fracture. The SRE is defined as the occurrence of either pathological or clinical fracture, spinal cord compression, radiation to bone, or surgery to bone.
  • Time to Chronic Opioid Use [ Time Frame: Up to 76 Months ]
    Time to chronic opioid use is defined as the time from date of randomization to the first date of opioid use or first date of an increase in the total daily dose.
  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to 76 Months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
Official Title  ICMJE A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Brief Summary The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.
Detailed Description This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. The radiographic progression-free survival or overall survival will be evaluated. Participants' safety will be monitored throughout the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Apalutamide
    Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
    Other Names:
    • JNJ-56021927
    • ARN-509
  • Drug: Placebo
    Participants will receive Placebo orally once daily in each 28 day treatment cycles.
  • Drug: Androgen Deprivation Therapy (ADT)
    All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.
Study Arms  ICMJE
  • Experimental: Apalutamide plus ADT
    Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.
    Interventions:
    • Drug: Apalutamide
    • Drug: Androgen Deprivation Therapy (ADT)
  • Experimental: Placebo plus ADT
    Participants will receive matching Placebo with ADT.
    Interventions:
    • Drug: Placebo
    • Drug: Androgen Deprivation Therapy (ADT)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 7, 2018)
1052
Original Estimated Enrollment  ICMJE
 (submitted: July 1, 2015)
1000
Estimated Study Completion Date  ICMJE July 12, 2021
Estimated Primary Completion Date November 4, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of prostate adenocarcinoma as confirmed by the investigator
  • Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1
  • Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization
  • Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization
  • Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies

Exclusion Criteria:

  • Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
  • Known brain metastases
  • Lymph nodes as only sites of metastases
  • Visceral (ie, liver or lung) metastases as only sites of metastases
  • Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
  • Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer
  • History of seizures or medications known to lower seizure threshold
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Hungary,   Israel,   Japan,   Korea, Republic of,   Mexico,   Poland,   Romania,   Russian Federation,   Spain,   Sweden,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02489318
Other Study ID Numbers  ICMJE CR107614
2015-000735-32 ( EudraCT Number )
56021927PCR3002 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aragon Pharmaceuticals, Inc.
Study Sponsor  ICMJE Aragon Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Aragon Pharmaceuticals, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP