This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT01193244
First received: August 31, 2010
Last updated: April 7, 2017
Last verified: April 2017
  Purpose
This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel (TAK-700) plus prednisone compared with placebo plus prednisone in the treatment of men with progressive, chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC)

Condition Intervention Phase
Prostate Cancer Drug: Orteronel Drug: Placebo Drug: Prednisone Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel Plus Prednisone With Placebo Plus Prednisone in Patients With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

Primary Outcome Measures:
  • Radiographic Progression-free Survival (rPFS) [ Time Frame: Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years) ]
    rPFS 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, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (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 Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment.

  • Overall Survival [ Time Frame: Baseline until death (up to 4.7 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.


Secondary Outcome Measures:
  • Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12 [ Time Frame: Week 12 ]
    The PSA50 is defined as a decline of at least 50 percent (%) from baseline.

  • Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12 [ Time Frame: Week 12 ]
    A favorable CTC count was defined as less than <5 counts per 7.5 milliliter (mL) in whole blood. An unfavorable CTC count was defined as greater than or equal to (>=) 5 counts/7.5 mL in whole blood.

  • Time to Pain Progression [ Time Frame: Baseline until End of treatment (EOT) (approximately up to 4.7 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. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 100 with lower scores being indicative of less pain or pain interference.

  • Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58) ]
  • Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3 [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58) ]
    Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE.

  • Number of Participants With TEAEs Related to Vital Signs [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58) ]
  • Number of Participants With TEAEs Related to Weight [ Time Frame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58) ]
  • Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline until EOT (approximately up to 4.7 years) ]
    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 percent 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 percent 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: Baseline up to EOT (Cycle 61 Day 58) ]
  • Worst Change From Baseline Over Time in Cardiac Ejection Fraction [ Time Frame: Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58) ]
    Worst change was defined as the worst overall change that occurred in cardiac ejection fraction at any measured time point.

  • Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation [ Time Frame: Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58) ]
  • Percentage of Participants With Skeletal Related Events (SRE) [ Time Frame: Baseline up to EOT (approximately up to 4.7 years) ]
    Skeletal related (SRE) event is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.

  • Time to SRE [ Time Frame: Baseline up to EOT (Cycle 61 Day 58) ]
    Time to SRE is defined as the time from randomization to SRE, or death due to any cause, whichever comes first. SRE is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.

  • Percentage of Participants Achieving PSA50 Response at Any Time During the Study [ Time Frame: Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37 ]
    The PSA50 is defined as a decline of PSA by 50 percent 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 is defined as a decline of PSA by 90 percent from baseline.

  • Percentage of Participants Achieving PSA90 Response at Any Time During the Study [ Time Frame: Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37 ]
    The PSA90 is defined as a decline of PSA by 90 percent 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 4.7 years) ]
    Time to PSA progression was defined as time from randomization to a PSA increase of 25 percent 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, compared to baseline PSA.

  • Time to Docetaxel Chemotherapy [ Time Frame: Baseline until start of docetaxel chemotherapy (up to 4.7 years) ]
    Time to docetaxel based chemotherapy is defined as the time from randomization to the start of docetaxel based chemotherapy for prostate cancer, regardless of whether the participant received concurrent orteronel or not. Deaths due to disease progression prior to Docetaxel based chemotherapy were considered as events.

  • Time to Subsequent Antineoplastic Therapy [ Time Frame: Baseline until start of subsequent antineoplastic therapy (up to 4.7 years) ]
    Time to subsequent antineoplastic therapy is defined as the time from randomization to the start of any alternate antineoplastic therapy for prostate cancer. Deaths due to disease progression prior to antineoplastic therapy for prostate cancer are considered as events. Otherwise, time to next therapy is censored at the date of death or the last date the participant was known to be alive or the data cutoff date, whichever is earlier.

  • Percentage of Participants With Objective Response [ Time Frame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years) ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. A 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 or short axis of lymph nodes.

  • Time to Deterioration in Global Health Status [ Time Frame: Baseline until EOT (approximately up to 4.7 years) ]
    Global health status deterioration is defined as a drop greater than 16 points from the baseline assessment, confirmed at least 3 weeks later, on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module 30 (EORTC QLQ-C30) index after the score has been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30 consists of 30 questions, where question 1 to 28 can be answered with 1: Not at all, 2: A little, 3: Quite a bit, 4: Very much and question 29 to 30 with 1: Very poor to 7: Excellent. For subscales a high score from 0-100 indicates: high global quality of life, high level of functioning (physical, role, emotional, cognitive, social) or a high level of symptoms (fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties).


Enrollment: 1560
Actual Study Start Date: October 1, 2010
Study Completion Date: April 7, 2016
Primary Completion Date: January 1, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Orteronel + prednisone Drug: Orteronel
Orteronel will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.
Drug: Prednisone
Prednisone will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.
Placebo Comparator: Placebo + prednisone Drug: Placebo
Placebo will be administered orally twice a day continuously throughout the study. Additionally, all patients will receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and a testosterone concentration of <50 ng/dL.
Drug: Prednisone
Prednisone will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

  • Voluntary written consent
  • Male patients 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
  • Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Even if surgically sterilized, patients must practice effective barrier contraception during the entire study treatment and for 4 months after the last dose of study drug, OR abstain from heterosexual intercourse
  • Meet screening laboratory values as specified in protocol
  • Stable medical condition

Exclusion Criteria:

Patients 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
  • Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug
  • Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study
  • Received prior chemotherapy for prostate cancer with exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening
  • Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the 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
  • Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction
  • 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
  • Uncontrolled nausea, vomiting or diarrhea
  • Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
  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: NCT01193244

  Show 245 Study Locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01193244     History of Changes
Other Study ID Numbers: C21004
2010-018661-35 ( EudraCT Number )
0991413276 ( Other Identifier: TCTIP )
10/H0406/75 ( Registry Identifier: NRES )
U1111-1181-0387 ( Registry Identifier: WHO )
Study First Received: August 31, 2010
Results First Received: April 7, 2017
Last Updated: April 7, 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Genital Diseases, Male
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 22, 2017