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Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab

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ClinicalTrials.gov Identifier: NCT01515189
Recruitment Status : Completed
First Posted : January 24, 2012
Results First Posted : March 24, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE January 18, 2012
First Posted Date  ICMJE January 24, 2012
Results First Submitted Date  ICMJE February 3, 2017
Results First Posted Date  ICMJE March 24, 2017
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE February 17, 2012
Actual Primary Completion Date February 6, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
Overall Survival (OS) [ Time Frame: Approximately 48 months (assessed up to February 2016) ]
OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median and associated 2-sided 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
Original Primary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
Overall Survival (OS) [ Time Frame: Approximately 44 months after the first subject is randomized ]
OS is defined for each subject as the time between randomization date and death. If a subject has not died, the subject will be censored at the time of last contact (last known alive date) OS will be assessed after 540 death events have occurred. Interim analysis after 360 deaths have occurred
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
  • Progression Free Survival (PFS) by mWHO Criteria [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    PFS was defined as the time between randomization date and the date of progression or death, whichever occurred first. A participant who died without reported prior progression was considered to have progressed on the date of death. For a participant who underwent resection post randomization, PFS was censored on last tumor assessment date prior to resection. For those who remained alive and had not progressed, PFS was censored on last evaluable tumor assessment date. Participants who had not died and had no recorded post-baseline tumor assessment were censored at the day of randomization. For participants who had Progressive Disease (PD) prior to Week 12 and a subsequent assessment of Stable Disease (SD), Partial Response (PR), or Complete Response (CR), the date of PD following response was used in the analysis of PFS; otherwise these participants were censored on the date of their last tumor assessment. Median and 2-sided 95% CIs were calculated with Brookmeyer Crowley method.
  • Best Overall Response Rate (BORR) by mWHO Criteria [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    BORR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR or PR, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for BOR, e.g. on account of missing or "not evaluable" assessments, was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the BORR endpoint). 95% 2-sided exact confidence intervals were computed using the method of Clopper and Pearson.
  • Disease Control Rate (DCR) by mWHO Criteria [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    DCR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR, PR or SD, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for Disease Control (DC), (e.g. on account of missing or "not evaluable" assessments), was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the DCR endpoint). 95% 2-sided exact confidence intervals were computed using the Clopper and Pearson method.
  • Duration of Response (DOR) by mWHO Criteria [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    Duration of response for participants whose BOR was CR or PR was defined as the time between the date measurement criteria were first met for overall response of PR or CR (whichever status was recorded first) and the date of disease progression or death (whichever occurred first). For participants who underwent tumor resection following response but prior to disease progression, duration of response was censored on the date of last evaluable tumor assessment prior to resection. For participants who had BOR of SD, PR or CR at Week 12, or a confirmed response of PR or CR before Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of response. For those participants who remained alive and had not progressed following response, duration of response was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer Crowley method.
  • Duration of Stable Disease by mWHO Criteria [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    Duration of stable disease was defined for participants whose BOR was SD as the time between when SD was first documented and the date of PD or death (whichever occurred first). For a participant who underwent tumor resection following Week 12 but prior to disease progression, duration of stable disease was censored on the date of the last evaluable tumor assessment prior to resection. For participants who had BOR of SD at Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of stable disease. For participants with BOR of SD who had not subsequently progressed and who remained alive, duration of stable disease was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
  • Rate of Overall Survival [ Time Frame: Approximately 66 months ]
    OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Survival rates were calculated based on Kaplan-Meier estimation with log-log transformed confidence intervals. The survival rate at x year(s) is defined as the probability that a subject is alive at x year(s) following randomization.
  • Overall Survival of Participants With Brain Metastases at Baseline [ Time Frame: From date of randomization until 540 death events occurred (approximately 48 months) ]
    OS for each participant with brain metastases at baseline was measured as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median OS, and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
  • Progression Free Survival (PFS) [ Time Frame: Approximately 44 months after the first subject is randomized ]
    PFS is defined for each subject as the time between randomization date and the date of progression or death, whichever occurs first PFS will be assessed after 540 death events have occurred
  • Best Overall Response Rate (BORR) [ Time Frame: Approximately 44 months after the first subject is randomized ]
    BORR is defined by treatment arm as the total number of randomized subjects in the arm whose Best Overall Response (BOR) is Complete Response (CR) or Partial Response (PR), divided by the total number of randomized subjects in the arm BORR will be assessed after 540 death events have occurred
  • Disease Control Rate (DCR) [ Time Frame: Approximately 44 months after the first subject is randomized ]
    DCR is as the total number of randomized subjects in each arm with BOR of CR, PR or Stable Disease (SD), divided by the total number of randomized subjects in the arm DCR will be assessed after 540 death events have occurred
  • Duration of Response [ Time Frame: Approximately 44 months after the first subject is randomized ]
    A subject's duration of response is defined as the time between the date measurement criteria are first met for overall response of PR or CR (whichever status is recorded first, and if subsequently confirmed) and the date of disease progression or death, whichever occurs first Duration of Response will be assessed after 540 death events have occurred
  • Duration of Stable Disease [ Time Frame: Approximately 44 months after the first subject is randomized ]
    Duration of stable disease is defined for subjects whose BOR is SD as the time between when SD is first documented and the date of Progressive Disease (PD) or death (whichever occurs first) Duration of Stable Disease will be assessed after 540 death events have occurred
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab
Official Title  ICMJE A Randomized Double-Blind Phase III Study of Ipilimumab Administered at 3 mg/kg Versus at 10 mg /kg in Subjects With Previously Treated or Untreated Unresectable or Metastatic Melanoma
Brief Summary The purpose of this study is to determine whether giving Ipilimumab at a dose of 10mg/kg will extend the lives of subjects with unresectable or metastatic melanoma more than giving Ipilimumab at a dose of 3 mg/kg
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE Biological: Ipilimumab
Other Names:
  • Yervoy
  • BMS-734016
Study Arms  ICMJE
  • Experimental: Arm 1: Ipilimumab (3 mg/kg)
    Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity
    Intervention: Biological: Ipilimumab
  • Experimental: Arm 2: Ipilimumab (10 mg/kg)
    Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity
    Intervention: Biological: Ipilimumab
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: June 1, 2017)
831
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2012)
700
Actual Study Completion Date  ICMJE August 17, 2017
Actual Primary Completion Date February 6, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Unresectable Stage III or Stage IV melanoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

  • Brain metastases with symptoms or requiring treatment
  • History of autoimmune disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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,   Austria,   Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Mexico,   Netherlands,   Norway,   Poland,   South Africa,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries Brazil,   Chile,   Czech Republic,   Russian Federation,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01515189
Other Study ID Numbers  ICMJE CA184-169
2011-004029-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date July 2019

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