PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma (PD-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01621490
First received: June 14, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate pharmacodynamic changes of Nivolumab and Nivolumab in combination with Ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced)


Condition Intervention Phase
Advanced Melanoma
Metastatic Melanoma
Biological: Nivolumab
Drug: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Exploratory Study of the Biologic Effects of Nivolumab and Ipilimumab Monotherapy and Nivolumab in Combination With Ipilimumab Treatment in Subjects With Advanced Melanoma (Unresectable or Metastatic)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Immunomodulatory effects of Nivolumab and Nivolumab in combination with Ipilimumab as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Pre-dose day 1 ] [ Designated as safety issue: No ]
  • Immunomodulatory effects of Nivolumab and Nivolumab in combination with Ipilimumab as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Up to day 57 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of Nivolumab, Ipilimumab and Nivolumab in combination with Ipilimumab as measured by the incidence of adverse events (AEs), serious AEs, death, and changes in vital signs [ Time Frame: Up to 100 days after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab, Ipilimumab and Nivolumab in combination with Ipilimumab as measured by laboratory test abnormalities [ Time Frame: Every 2 or 3 weeks up to 100 days after last treatment ] [ Designated as safety issue: Yes ]
  • Antitumor Activity of Nivolumab and Nivolumab in combination with Ipilimumab as measured by the objective response rate (ORR), duration of response, and progression free survival (PFS) [ Time Frame: Approximately every 8 weeks until disease progression and in follow-up if no progression ] [ Designated as safety issue: No ]
  • Immunogenicity of Nivolumab and Nivolumab in combination with Ipilimumab as measured by the frequency of baseline positive subjects and the frequency of ADA positive subjects [ Time Frame: Up to follow-up visit 2 (101-120 days since last treatment) ] [ Designated as safety issue: Yes ]

    Time Frame:

    Part 1: Day 1, Day 15, Day 43 of cycle 1, Day 1 of cycle 2, Day 15 of cycle 3, every 16 weeks after cycle 3 up to 2 years, follow-up visit 1 (40-60 days after last treatment), and follow-up visit 2 (101-120 days since last treatment)

    Part 2, 3 and 4: Weeks 1, 3, 4, 7, 9, 10, 13, 25, 53, 79, 95 follow-up visit 1 (40-60 days after last treatment), and follow-up visit 2 (101-120 days since last treatment)


  • Association between Programmed cell death ligand 1 (PD-L1) and clinical efficacy will be measured by PDL1 expression levels clinical activity (ORR, PFS) [ Time Frame: Part 1: Pre-dose up to Day 1 (screening Day -7 to day 1 predose) and Day 29 of cycle 1. Part 2, 3 and 4: Pre-dose (screening Day -28 to Day 1 predose) and week 2 or 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: September 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1-Cohort 1 and 2: Nivolumab
Nivolumab 3 mg/kg solution intravenously Every 2 weeks, Up to 2 years depending on response
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)
Experimental: Part 2-Arm A: Nivolumab + Ipilimumab
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)
Drug: Ipilimumab
Other Names:
  • BMS734016
  • Yervoy
Experimental: Part 3-Arm A: Nivolumab + Ipilimumab
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)
Drug: Ipilimumab
Other Names:
  • BMS734016
  • Yervoy
Experimental: Part 3-Arm B: Nivolumab
Nivolumab 3 mg/kg solution intravenously as specified
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)
Experimental: Part 3-Arm C: Ipilimumab
Ipilimumab 3 mg/kg solution intravenously as specified
Drug: Ipilimumab
Other Names:
  • BMS734016
  • Yervoy
Experimental: Part 4-Arm D: Nivolumab + Ipilimumab
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)
Drug: Ipilimumab
Other Names:
  • BMS734016
  • Yervoy
Experimental: Part 4-Arm E: Nivolumab
Nivolumab 3 mg/kg solution intravenously as specified
Biological: Nivolumab
Other Name: BMS-936558 (MDX1106)

Detailed Description:

Allocation:

Part 1 and 2: Single Arm study

Part 3 and 4: Randomized Controlled Trial

Intervention Model:

Part 1 and 2: Single group: Single arm study

Part 3 and 4: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Minimum Age:

Part 1: 18

Part 2, 3 and 4: 16

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Part 1:

Inclusion Criteria:

  • Men and women >18 years
  • Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
  • Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
  • Subject must have histologic or cytologic confirmation of advanced melanoma
  • Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

Exclusion Criteria:

  • Active or progressing brain metastases
  • Other concomitant malignancies (with some exceptions per protocol)
  • Active or history of autoimmune disease
  • Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
  • History of any hepatitis
  • Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy

Part 2, 3 and 4:

Inclusion Criteria

  • Men and women >16 years
  • Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
  • Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
  • Subjects must never received anti-CTLA4 therapy
  • Subjects must have histologic or cytologic confirmation of advanced melanoma
  • Subjects must have at least two measurable lesions at baseline by CT or MRI as per RECIST 1.1 criteria
  • Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
  • Subjects in Part 4 must have brain metastases

Exclusion Criteria

  • Active or progressing brain metastases (except for Part 4 subjects)
  • Other concomitant malignancies (with some exceptions per protocol)
  • Active or history of autoimmune disease
  • Positive test for HIV 1&2 or known AIDS
  • History of any hepatitis
  • Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies
  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: NCT01621490

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, California
Local Institution Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Site 0015         
United States, Illinois
University Of Chicago Active, not recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Recruiting
Lutherville, Maryland, United States, 21093
Contact: William Sharfman, Site 0005    443-287-6122      
United States, Massachusetts
Dana Farber Cancer Institute Active, not recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Ctr Recruiting
New York, New York, United States, 10065
Contact: Jedd Wolchok, Site 0009    646-227-2177      
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Walter J Urba, Site 0001    503-215-2619      
United States, Tennessee
Vanderbilt-Ingram Cancer Ctr Active, not recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
The University Of Texas Md Anderson Cancer Center Active, not recruiting
Houston, Texas, United States, 77030
United States, Virginia
University Of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Craig Slingluff, Site 0004    434-982-6714      
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Shailender Bhatia, Site 0003    206-288-7476      
Netherlands
Local Institution Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Site 0016         
Spain
Local Institution Recruiting
Pamplona, Spain, 31192
Contact: Site 0008         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01621490     History of Changes
Other Study ID Numbers: CA209-038, 2012-001840-23
Study First Received: June 14, 2012
Last Updated: August 4, 2014
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

ClinicalTrials.gov processed this record on August 27, 2014