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
  Purpose
The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab

Condition Intervention Phase
Advanced or Metastatic Melanoma
Biological: Nivolumab
Biological: Ipilimumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 177
Study Start Date: April 2013
Estimated Study Completion Date: April 2017
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Other Name: Yervoy
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.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Other Name: Yervoy

Detailed Description:
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.
  Eligibility

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

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
  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: NCT01783938

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University Health Melvin And Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18103
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
University Of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01783938     History of Changes
Other Study ID Numbers: CA209-064 
Study First Received: February 1, 2013
Results First Received: March 11, 2016
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2016