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Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01783938
First received: February 1, 2013
Last updated: April 11, 2016
Last verified: April 2016

February 1, 2013
April 11, 2016
April 2013
April 2015   (final data collection date for primary outcome measure)
Percentage of Participants With Treatment-related Grade 3-5 Adverse Events (AEs) During the Induction Periods [ Time Frame: Day 1 up to Week 25 ] [ Designated as safety issue: Yes ]
The rate or percentage of participants with treatment-related grade 3-5 AEs is defined as the number of participants who experienced at least 1 treatment related Grade 3 - 5 adverse event (AE) per NCI CTCAE version 4.0 criteria, any preferred term with an onset date after or on first day of Induction Period #1 and not later than discontinuation date from Induction Period #2, divided by the total number of treated participants. AEs with an onset date after start date of Continuation Period or start of subsequent anti-cancer therapy were not included. Adverse Event (AE)=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Potentially Life-threatening or disabling, Gr 5=Death.
Incidence of treatment-related grade 3-5 adverse events (AEs) during the induction period [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01783938 on ClinicalTrials.gov Archive Site
  • Investigator-assessed Response Rate at Week 25 [ Time Frame: Week 25 ] [ Designated as safety issue: No ]
    Response rate is defined as the number of participants who have a complete response (CR) or partial response (PR) at Week 25 per modified RECIST 1.1 criteria, with confirmation on the scheduled scan at Week 33 (or any subsequent scan performed at least 4 weeks after the Week 25 scan), divided by the total number of treated participants. Results of the tumor assessment at Week 13 or any unscheduled tumor assessment obtained prior to Week 25, except for baseline/screening tumor assessment, were not considered in the assessment of response rate at Week 25. Any treated participant without an evaluable Week 25 time point response (per modified RECIST 1.1) was considered a non-responder for primary analysis of response rate at Week 25. Evaluations occurring after the dates of subsequent anticancer therapy were not included when determining or confirming response at Week 25. Confidence interval based on the Clopper and Pearson method.
  • Investigator-assessed Duration of Response (DOR) [ Time Frame: Week 25 up to date of disease progression or death, up to approximately 2 years ] [ Designated as safety issue: No ]
    Duration of response (DOR) was performed to further characterize the response rate at Week 25. Duration of response is defined as the time between the Week 25 date of response and the date of objectively documented disease progression as defined by modified RECIST 1.1 criteria or death, whichever occurs first. DOR was assessed for participants with confirmed response at Week 25. Median computed using Kaplan-Meier product-limit method.
  • Investigator-assessed Rate of Progression [ Time Frame: Week 13; Week 25 ] [ Designated as safety issue: No ]
    The progression rate at a specific timepoint is defined as the number of participants who have Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at that specific timepoint divided by the total number of randomized participants. As specified by modified RECIST 1.1, the evaluation of PD at Week 13 and Week 25 used the baseline tumor assessment as reference. For purposes of the primary analysis of progression rates, if a treated participant were missing his/her tumor assessment at the specified study week, then the results of the previous tumor response evaluation were to be carried forward. Both clinical and radiological progressions were counted as a progression outcome. A participant who died without a reported prior progression was considered to have progressed on the date of his/her death. Deaths before or at Week 13 are counted as progression outcome. Confidence interval based on the Clopper and Pearson method.
  • Response rate [ Time Frame: Baseline (Day 1), Week 25 and Week 33 ] [ Designated as safety issue: No ]
    Response rate is defined as the number of subjects who have a complete response (CR) or partial response (PR) at Week 25 (with confirmation at scheduled scan at Week 33) divided by the total number of randomized subjects
  • Progression rates [ Time Frame: Baseline (Day 1), Week 13 and Week 25 ] [ Designated as safety issue: No ]
    Progression rate at a specific timepoint is defined as the number of subjects who have Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at that specific timepoint divided by the total number of randomized subjects
Not Provided
Not Provided
 
Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)
An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma
The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab
In order to evaluate the potential synergistic activity of nivolumab and ipilimumab and also because there may be differences in biology between tumors which are stable or responding to therapy and those that are clinically progressing, this study, CA209064, looked at two sequential combination regimens in which the second agent is administered immediately after a pre-specified duration of therapy with the first agent and not delayed until the time of progression after the first agent. This sequential study design looked at pharmacodynamic changes during treatment with one agent which may predict clinical activity to subsequent treatment with the alternate agent. This was done because it has not been scientifically proven whether or not the order in which nivolumab and ipilimumab are given is clinically important.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced or Metastatic Melanoma
  • Biological: Nivolumab
    Other Name: BMS-936558
  • Biological: Ipilimumab
    Other Name: Yervoy
  • Experimental: Cohort A: Nivolumab followed by Ipilimumab

    Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1.

    Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period.

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Cohort B: Ipilimumab followed by Nivolumab

    Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period.

    Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1.

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
177
April 2017
April 2015   (final data collection date for primary outcome measure)

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

Inclusion Criteria:

  • Histologically confirmed unresectable Stage III or IV melanoma
  • Treatment-naive or experienced disease recurrence or progression during or after one prior systemic regimen for advanced disease
  • Measurable disease by Computed Tomography/Magnetic resonance imaging (CT/MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Known BRAF V600 mutation status or consent to BRAF V600 mutation testing
  • Sufficient tumor tissue accessible for baseline and post-treatment biopsies.

Exclusion Criteria:

  • Active central nervous system (CNS) metastases
  • Carcinomatous meningitis
  • Active, known or suspected autoimmune disease
  • Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
  • Prior therapy with anti-Programmed Death-1 (PD1), anti-Programmed Death-Ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-CTLA-4 (cytotoxic T lymphocyte antigen 4) antibody
  • Prior treatment with other immunotherapies
  • Prior therapy with BRAF inhibitor within 6 weeks of enrollment
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01783938
CA209-064
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
April 2016

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