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Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer.

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: NCT01193257
Recruitment Status : Completed
First Posted : September 1, 2010
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE August 31, 2010
First Posted Date  ICMJE September 1, 2010
Results First Submitted Date  ICMJE February 27, 2017
Results First Posted Date  ICMJE December 19, 2018
Last Update Posted Date December 19, 2018
Actual Study Start Date  ICMJE November 15, 2010
Actual Primary Completion Date May 16, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
Overall Survival [ Time Frame: Baseline until death (approximately up to 4.5 years) ]
Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.
Original Primary Outcome Measures  ICMJE
 (submitted: August 31, 2010)
To determine if orteronel plus prednisone improves overall survival (OS) [ Time Frame: Time from patient randomization to death from any cause ]
Patients will be followed for survival until 80% of patients have died or are lost to follow-up
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • Radiographic Progression-free Survival (rPFS) [ Time Frame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years) ]
    rPFS was defined as the time from randomization until radiographic disease progression or death due to any cause, whichever occurred first. Radiographic disease progression was defined as the occurrence of 1 or more of the following: The appearance of 2 or more new lesions on radionuclide bone scan as defined by prostate cancer working group (PCWG)2; Should 2 or more new bone lesions be evident at the first assessment (8-week assessment) on treatment, 2 or more additional new lesions must have been evident on a confirmatory assessment at least 6 weeks later; One or more new soft tissue/visceral organ lesions identified by computed tomography (CT)/magnetic resonance imaging (MRI); Progression as defined by response evaluation criteria in solid tumors (RECIST) 1.1 criteria.
  • Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12 [ Time Frame: Week 12 ]
    The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50 percent (%) from baseline.
  • Percentage of Participants With Pain Response at Week 12 [ Time Frame: Week 12 ]
    Pain response was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: A greater than or equal to (>=) 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use; or a 25 percent (%) or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.
  • Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58) ]
  • Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58) ]
  • Number of Participants With TEAEs Related to Vital Signs [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58) ]
  • Number of Participants With TEAEs Related to Weight [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58) ]
  • Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline up to End-of-treatment (EOT) (Cycle 59 Day 58) ]
    ECOG assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Worst change was defined as the worst overall change that occurred in ECOG status at any measured time point during the treatment period.
  • Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Cycle 59 Day 58 ]
  • Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58) ]
  • Percentage of Participants Achieving PSA50 Response at Any Time During the Study [ Time Frame: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25 ]
    The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline.
  • Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12 [ Time Frame: Week 12 ]
    The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.
  • Percentage of Participants Achieving PSA90 Response at Any Time During the Study [ Time Frame: Cycle: 7, 10, 13, 16, 19, 22, and 25 ]
    The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.
  • Best PSA Response at Any Time During the Study [ Time Frame: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25 ]
    The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline. PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.
  • Time to PSA Progression [ Time Frame: Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.5 years) ]
    Time to PSA progression was defined as time from randomization to a PSA increase of 25% and PSA rise of at least 2 nanogram per milliliter (ng/mL) above the lowest value observed post baseline or, if no PSA decline occurred post baseline, above the baseline PSA.
  • Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) [ Time Frame: Baseline and EOT (Cycle 59 Day 58) ]
    A favorable CTC count was defined as less than (<) 5 counts per (/) 7.5 mililiter (mL) in whole blood. An unfavorable CTC count was defined as >=5 counts/7.5 mL in whole blood.
  • Percentage of Participants With Objective Response [ Time Frame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years) ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. The overall objective response was defined as a complete response (CR) or partial response (PR). A complete response (CR) was defined as the disappearance of all target lesions determined by computerized tomography (CT) or MRI. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 millimetre (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes.
  • Time to Pain Progression [ Time Frame: Baseline until EOT visit or until end of short term follow-up, whichever occurred later (approximately up to 4.5 years) ]
    Time to pain progression was defined as the time from participant randomization to the first assessment date of pain progression. Pain progression was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: The brief pain inventory-short form (BPI-SF) worst pain score was >= 4 with a >= 2 point increase over baseline in BPI-SF worst pain score with stable or increased analgesic use; The BPI-SF worst pain score was >= 4 but not less than baseline with new or increased (relative to baseline) Step II or Step III analgesic use; The BPI-SF worst pain score was <= 3 but not less than baseline with new or increased (relative to baseline) Step III analgesic use.
  • Time to Pain Response [ Time Frame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years) ]
    Time to pain response was defined as the time from randomization until first pain response. Pain response was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: A >= 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline. The analysis was performed by Kaplan-Meier method.
  • Number of Participants With Best Pain Response [ Time Frame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years) ]
    Best pain response was evaluated in participants who had a pain response across the entire study were summarized by treatment group. The pain response was defined as a >=2-point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.
  • Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12 [ Time Frame: Week 12 ]
    The global health status or quality of life (QOL) was measured as the HRQOL response rate at 12 weeks using the 2-item global health status index of the european organization for research and treatment of cancer-quality of life questionnaire-C30 (EORTC QLQ-C30) instrument. HRQOL response was defined as a 17-point increase from the baseline assessment on the QOL index, after the score had been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status, 3 symptom scales (fatigue, pain, nausea/vomiting) and 6 single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score representing better level of functioning or greater degree of symptoms.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2010)
  • To determine if orteronel plus prednisone improves 50% prostate specific antigen (PSA) response at 12 weeks [ Time Frame: 12 weeks ]
  • To evaluate whether orteronel plus prednisone improves pain response at 12 weeks [ Time Frame: 12 weeks ]
  • To determine if orteronel plus prednisone improves radiographic progression-free survival (rPFS) [ Time Frame: Time from patient randomization to radiographic disease progression or death from any cause, whichever occurs first ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer.
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or Following Docetaxel-based Therapy.
Brief Summary This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel plus prednisone compared with placebo plus prednisone in men with metastatic, castration-resistant prostate cancer (mCRPC) that has progressed following Docetaxel-based therapy
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Orteronel
    Orteronel tablets
    Other Name: TAK-700
  • Drug: Prednisone
    Prednisone tablets
  • Drug: Orteronel Placebo
    Orteronel placebo-matching tablets
Study Arms  ICMJE
  • Experimental: Orteronel + prednisone
    Interventions:
    • Drug: Orteronel
    • Drug: Prednisone
  • Placebo Comparator: Placebo + prednisone
    Interventions:
    • Drug: Prednisone
    • Drug: Orteronel Placebo
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 Completed
Actual Enrollment  ICMJE
 (submitted: August 1, 2013)
1099
Original Estimated Enrollment  ICMJE
 (submitted: August 31, 2010)
1083
Actual Study Completion Date  ICMJE February 29, 2016
Actual Primary Completion Date May 16, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria:

  • Voluntary written consent
  • Male 18 years or older
  • Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
  • Radiograph-documented metastatic disease
  • Progressive disease
  • Prior surgical castration or concurrent use of an agent for medical castration
  • Progressive disease during or following 1 or 2 regimens of cytotoxic chemotherapy, 1 of which must have included docetaxel. Must have received greater than or equal to (>=) 360 milligram per square meter (mg/m^2) of docetaxel within a 6-month period. Participants who were clearly intolerant to docetaxel or develop progressive disease before receiving >= 360 mg/m^2 are also eligible if they have received at least 225 mg/m^2 of docetaxel within a 6-month period and meet the other study entry criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Even if surgically sterilized, participants must practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, OR Abstain from heterosexual intercourse
  • Screening laboratory values as specified in protocol
  • Stable medical condition
  • Life expectancy of 6 months or more
  • Participants who have had up to 2 prior chemotherapy treatments are eligible to participate

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue
  • Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone
  • Any other therapies for prostate cancer, except for GnRH analogue therapy, must be discontinued 2 weeks before the first dose of study drug
  • Radioisotope therapy or external beam radiation therapy within 4 weeks of first dose of study drug
  • Documented central nervous system metastases
  • Treatment with any investigational compound within 30 days prior to first dose of study drug (Participants who are in long-term follow-up following active treatment in other trials are eligible)
  • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
  • Uncontrolled cardiovascular condition as specified in study protocol
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
  • Unwilling or unable to comply with protocol
  • Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
  • Uncontrolled nausea, vomiting, or diarrhea despite appropriate medical therapy
  • Prostate cancer confined to just the prostrate bed or immediate adjacent tissue
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 Australia,   Belgium,   Canada,   Czechia,   Estonia,   Finland,   France,   Greece,   Hungary,   Italy,   Netherlands,   Poland,   Spain,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01193257
Other Study ID Numbers  ICMJE C21005
2010-018662-23 ( EudraCT Number )
CTR20131423 ( Registry Identifier: SFDA CTR )
0991413212 ( Registry Identifier: TCTIN )
C21005 ( Registry Identifier: NRES )
U1111-1181-8040 ( Registry Identifier: WHO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
PRS Account Takeda
Verification Date November 2018

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