Clinical trial NCT01927419: Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma
Official title: Phase 2, Randomized, Double Blinded, Study of Nivolumab (BMS-936558) in Combination With Ipilimumab vs Ipilimumab Alone in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Unresectable Melanoma
Metastatic Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-08-22
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants
timeFrame: 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:
measure: Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants
timeFrame: From randomization to progression or death (up to approximately 88 months)
measure: Objective Response Rate (ORR) - BRAF Mutant Participants
timeFrame: 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)
measure: Progression-Free Survival (PFS) - BRAF Mutant Participants
timeFrame: From randomization to progression or death (up to approximately 88 months)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score
timeFrame: From Baseline (prior to start of study treatment) to Week 25 after first dose
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Oncology Associates
state: California
city: Orlando
country: United States
facility: Orlando Health Inc
state: Florida
city: Louisville
country: United States
facility: University Of Louisville Medical Center, Inc., Dba
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers Of Nevada
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albuquerque
country: United States
facility: University Of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Easton
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: GHS Cancer Institute
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Madison
country: United States
facility: University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr
state: Wisconsin
city: Toulouse
country: France
facility: Hopital Larrey
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.