NCT01927419

Brief Summary

The primary purpose of this study is to compare the objective response rate, as determined by investigators, of Nivolumab combined with Ipilimumab versus Ipilimumab monotherapy in patients with untreated, unresectable, or metastatic melanoma

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
142

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2013

Longer than P75 for phase_2

Geographic Reach
2 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 20, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 22, 2013

Completed
1 day until next milestone

Study Start

First participant enrolled

August 23, 2013

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2014

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

February 8, 2016

Completed
5.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 26, 2021

Completed
Last Updated

March 18, 2022

Status Verified

February 1, 2022

Enrollment Period

11 months

First QC Date

August 20, 2013

Results QC Date

November 3, 2015

Last Update Submit

February 16, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants

    Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria. CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (\<10 mm). PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)

Secondary Outcomes (4)

  • Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants

    From randomization to progression or death (up to approximately 88 months)

  • Objective Response Rate (ORR) - BRAF Mutant Participants

    From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)

  • Progression-Free Survival (PFS) - BRAF Mutant Participants

    From randomization to progression or death (up to approximately 88 months)

  • Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score

    From Baseline (prior to start of study treatment) to Week 25 after first dose

Study Arms (2)

Nivolumab + Ipilimumab

EXPERIMENTAL

Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Drug: NivolumabDrug: Ipilimumab

Placebo + Ipilimumab

EXPERIMENTAL

Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Drug: IpilimumabDrug: Placebo

Interventions

Also known as: Opdivo, BMS-936558
Nivolumab + Ipilimumab
Also known as: Yervoy
Nivolumab + IpilimumabPlacebo + Ipilimumab

Matching nivolumab

Placebo + Ipilimumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Histologically confirmed unresectable Stage III or Stage IV melanoma
  • No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
  • Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
  • Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.

You may not qualify if:

  • Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (\>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
  • Ocular melanoma
  • Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

San Francisco Oncology Associates

San Francisco, California, 94115, United States

Location

Orlando Health Inc

Orlando, Florida, 32806, United States

Location

University Of Louisville Medical Center, Inc., Dba

Louisville, Kentucky, 40202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers Of Nevada

Las Vegas, Nevada, 89148, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University Of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Nassau

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital

Easton, Pennsylvania, 18045, United States

Location

GHS Cancer Institute

Greenville, South Carolina, 29615, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr

Madison, Wisconsin, 53792, United States

Location

Hopital Larrey

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (4)

  • Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.

  • Mantia CM, Werner L, Stwalley B, Ritchings C, Tarhini AA, Atkins MB, McDermott DF, Regan MM. Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors. Melanoma Res. 2022 Feb 1;32(1):35-44. doi: 10.1097/CMR.0000000000000793.

  • Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1558-1568. doi: 10.1016/S1470-2045(16)30366-7. Epub 2016 Sep 9.

  • Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015 May 21;372(21):2006-17. doi: 10.1056/NEJMoa1414428. Epub 2015 Apr 20.

Related Links

MeSH Terms

Conditions

Melanoma

Interventions

NivolumabIpilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Bristol-Myers Squibb Study Director
Organization
Bristol-Myers Squibb

Study Officials

  • Bristol-Myers Squibb

    Bristol-Myers Squibb

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 20, 2013

First Posted

August 22, 2013

Study Start

August 23, 2013

Primary Completion

July 24, 2014

Study Completion

February 26, 2021

Last Updated

March 18, 2022

Results First Posted

February 8, 2016

Record last verified: 2022-02

Locations