Clinical trial NCT02388906: Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma
Official title: A Phase 3, Randomized, Double-blind Study of Adjuvant Immunotherapy With Nivolumab Versus Ipilimumab After Complete Resection of Stage IIIb/c or Stage IV Melanoma in Subjects Who Are at High Risk for Recurrence (CheckMate 238: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 238)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2015-03-17
Enrollment: 906
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.


Eligibility criteria: Inclusion Criteria:

* At least 15 years of age Except: where local regulations and/or institutional policies do not allow for subjects \< 18 years of age (pediatric population) to participate. For those sites, the eligible subject population is ≥ 18 years of age
* Completely removed melanoma by surgery performed within 12 weeks of randomization
* Stage IIIb/C or Stage IV before complete resection
* No previous anti-cancer treatment

Exclusion Criteria:

* Ocular or uveal melanoma
* History of carcinomatosis meningitis
* History of auto-immune disease
* Treatment directed against the resected melanoma that is administrated after the surgery

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Recurrence-free Survival (RFS)
timeFrame: up to 36 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 106.6 months
measure: The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
timeFrame: reported between first dose and 30 days after last dose of study therapy
measure: The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events
timeFrame: reported between the first dose and 30 days after last dose of study therapy
measure: the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths
timeFrame: reported between first dose and 30 to 100 days after last dose of study therapy
measure: The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities
timeFrame: reported after first dose and within 30 days of last dose of the study therapy
measure: Recurrence-free Survival by PD-L1 Expression
timeFrame: up to 106.6 months
measure: Health Related Quality of Life (HRQoL) Evaluation
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Local Institution - 0036
state: Arkansas
city: La Jolla
country: United States
facility: Local Institution - 0117
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0189
state: California
city: San Francisco
country: United States
facility: Local Institution - 0021
state: California
city: San Francisco
country: United States
facility: Local Institution - 0006
state: California
city: Aurora
country: United States
facility: Local Institution - 0010
state: Colorado
city: Washington
country: United States
facility: Local Institution - 0004
state: District of Columbia
city: Jacksonville
country: United States
facility: Local Institution - 0012
state: Florida
city: Miami Beach
country: United States
facility: Local Institution - 0019
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0030
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0032
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0016
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0106
state: Illinois
city: Boston
country: United States
facility: Local Institution - 0013
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0170
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0171
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0015
state: Michigan
city: Robbinsdale
country: United States
facility: Local Institution - 0002
state: Minnesota
city: Saint Louis
country: United States
facility: Local Institution - 0017
state: Missouri
city: Hackensack
country: United States
facility: Local Institution - 0123
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution - 0095
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0024
state: New York
city: New York
country: United States
facility: Local Institution - 0033
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0003
state: North Carolina
city: Durham
country: United States
facility: Local Institution - 0025
state: North Carolina
city: Columbus
country: United States
facility: Local Institution - 0157
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0031
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0029
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0022
state: Pennsylvania
city: Bethlehem
country: United States
facility: Local Institution - 0001
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0026
state: South Carolina
city: Nashville
country: United States
facility: Local Institution - 0014
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0005
state: Texas
city: Charlottesville
country: United States
facility: Local Institution - 0027
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 0126
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution - 0142
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Local Institution - 0140
state: Tucuman
city: Cordoba
country: Argentina
facility: Local Institution
city: Gateshead
country: Australia
facility: Local Institution - 0079
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0080
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Local Institution - 0078
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution - 0082
state: Queensland
city: Southport
country: Australia
facility: Local Institution - 0083
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 0084
state: South Australia
city: Heidelberg
country: Australia
facility: Local Institution - 0075
state: Victoria
city: Prahran
country: Australia
facility: Local Institution - 0077
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0085
state: Western Australia
city: Camperdown
country: Australia
facility: Local Institution - 0081
city: Graz
country: Austria
facility: Local Institution - 0169
city: Salzburg
country: Austria
facility: Local Institution - 0168
city: Brussels
country: Belgium
facility: Local Institution - 0038
city: Bruxelles
country: Belgium
facility: Local Institution - 0040
city: Gent
country: Belgium
facility: Local Institution - 0037
city: Leuven
country: Belgium
facility: Local Institution - 0039
city: Edmonton
country: Canada
facility: Local Institution - 0051
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 0074
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0094
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0105
state: Quebec
city: Quebec City
country: Canada
facility: Local Institution - 0046
state: Quebec
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0101
city: Ostrava-Poruba
country: Czechia
facility: Local Institution - 0102
city: Praha 1
country: Czechia
facility: Local Institution - 0099
city: Praha 2
country: Czechia
facility: Local Institution - 0100
city: Helsinki
country: Finland
facility: Local Institution - 0047
city: Tampere
country: Finland
facility: Local Institution - 0048
city: Lille
country: France
facility: Local Institution - 0138
city: Marseille Cedex 5
country: France
facility: Local Institution - 0135
city: Nantes
country: France
facility: Local Institution - 0134
city: Paris
country: France
facility: Local Institution - 0136
city: Pierre Benite
country: France
facility: Local Institution - 0133
city: Toulouse
country: France
facility: Local Institution - 0137
city: Athens
country: Greece
facility: Local Institution - 0086
city: Neo Faliro
country: Greece
facility: Local Institution - 0087
city: Budapest
country: Hungary
facility: Local Institution - 0163
city: Dublin 7
country: Ireland
facility: Local Institution - 0166
city: Dublin
country: Ireland
facility: Local Institution - 0063
city: Dublin
country: Ireland
facility: Local Institution - 0108
city: Galway
country: Ireland
facility: Local Institution - 0064
city: Bergamo
country: Italy
facility: Local Institution - 0112
city: Genova
country: Italy
facility: Local Institution - 0116
city: Meldola (FC)
country: Italy
facility: Local Institution - 0115
city: Milano
country: Italy
facility: Local Institution - 0113
city: Napoli
country: Italy
facility: Local Institution - 0107
city: Padova
country: Italy
facility: Local Institution - 0111
city: Roma
country: Italy
facility: Local Institution - 0114
city: Siena
country: Italy
facility: Local Institution - 0110
city: Nagoya
country: Japan
facility: Local Institution - 0179
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0161
state: Fukuoka
city: Tsukuba-shi
country: Japan
facility: Local Institution - 0174
state: Ibaraki
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0162
state: Kumamoto
city: Matsumoto
country: Japan
facility: Local Institution - 0160
state: Nagano
city: Niigata-shi
country: Japan
facility: Local Institution - 0175
state: Niigata
city: Osaka-shi
country: Japan
facility: Local Institution - 0176
state: Osaka
city: Sunto-gun
country: Japan
facility: Local Institution - 0159
state: Shizuoka
city: Chuo-ku
country: Japan
facility: Local Institution - 0158
state: Tokyo
city: Chuo-shi
country: Japan
facility: Local Institution - 0180
state: Yamanashi
city: Songpa-gu
country: Korea, Republic of
facility: Local Institution - 0144
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0129
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0127
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0128
city: Amsterdam
country: Netherlands
facility: Local Institution - 0042
city: Groningen
country: Netherlands
facility: Local Institution - 0045
city: Nijmegen
country: Netherlands
facility: Local Institution - 0043
city: Veldhoven
country: Netherlands
facility: Local Institution - 0041
city: Bergen
country: Norway
facility: Local Institution - 0098
city: Oslo
country: Norway
facility: Local Institution - 0109
city: Gdansk
country: Poland
facility: Local Institution - 0150
city: Krakow
country: Poland
facility: Local Institution - 0149
city: Warszawa
country: Poland
facility: Local Institution - 0152
city: Craiova
country: Romania
facility: Local Institution - 0156
city: Romania
country: Romania
facility: Local Institution - 0153
city: Johannesburg
country: South Africa
facility: Local Institution - 0148
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution - 0145
state: Gauteng
city: Saxonwold, Johannesburg
country: South Africa
facility: Local Institution - 0147
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution - 0181
state: Western CAPE
city: Kraaifontein
country: South Africa
facility: Local Institution - 0146
state: Western Cape
city: Barcelona
country: Spain
facility: Local Institution - 0120
city: Madrid
country: Spain
facility: Local Institution - 0119
city: Sevilla
country: Spain
facility: Local Institution - 0121
city: Valencia
country: Spain
facility: Local Institution - 0122
city: Gothenberg
country: Sweden
facility: Local Institution - 0050
city: Lund
country: Sweden
facility: Local Institution - 0096
city: Zuerich
country: Switzerland
facility: Local Institution - 0167
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0131
city: Taichung
country: Taiwan
facility: Local Institution - 0132
city: Taoyuan
country: Taiwan
facility: Local Institution - 0130
city: Bristol
country: United Kingdom
facility: Local Institution - 0057
state: Avon
city: Swansea
country: United Kingdom
facility: Local Institution - 0052
state: Carmarthenshire
city: London
country: United Kingdom
facility: Local Institution - 0165
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution - 0054
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Local Institution - 0056
state: Hampshire
city: Northwood
country: United Kingdom
facility: Local Institution - 0177
state: Middlesex
city: Oxford
country: United Kingdom
facility: Local Institution - 0055
state: Oxfordshire
city: Newcastle Upon Tyne
country: United Kingdom
facility: Local Institution - 0060
state: Tyne And Wear
city: Leicester
country: United Kingdom
facility: Local Institution - 0097
city: Surrey
country: United Kingdom
facility: Local Institution - 0053
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Larkin J, Weber J, Del Vecchio M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Middleton MR, De la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Long GV, Lobo M, Askelson M, Ascierto PA, Mandala M. Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria. Eur J Cancer. 2022 Sep;173:285-296. doi: 10.1016/j.ejca.2022.06.041. Epub 2022 Aug 11.
citation: Weber JS, Ascierto PA, Middleton MR, Hennicken D, Zoffoli R, Pieters A, Amadi A, Kupas K, Kotapati S, Moshyk A, Schadendorf D. Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. Eur J Cancer. 2021 Nov;158:225-233. doi: 10.1016/j.ejca.2021.08.028. Epub 2021 Oct 15.
citation: Mandala M, Larkin J, Ascierto PA, Del Vecchio M, Gogas H, Cowey CL, Arance A, Dalle S, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Lutzky J, De La Cruz-Merino L, Atkinson V, Arenberger P, Hill A, Fecher L, Millward M, Khushalani NI, de Pril V, Lobo M, Weber J. Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. J Immunother Cancer. 2021 Aug;9(8):e003188. doi: 10.1136/jitc-2021-003188.
citation: Ascierto PA, Del Vecchio M, Mandala M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Maio M, Middleton MR, de la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Lobo M, de Pril V, Loffredo J, Larkin J, Weber J. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1465-1477. doi: 10.1016/S1470-2045(20)30494-0. Epub 2020 Sep 19.
citation: Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S, Schenker M, Chiarion-Sileni V, Marquez-Rodas I, Grob JJ, Butler MO, Middleton MR, Maio M, Atkinson V, Queirolo P, Gonzalez R, Kudchadkar RR, Smylie M, Meyer N, Mortier L, Atkins MB, Long GV, Bhatia S, Lebbe C, Rutkowski P, Yokota K, Yamazaki N, Kim TM, de Pril V, Sabater J, Qureshi A, Larkin J, Ascierto PA; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9;377(19):1824-1835. doi: 10.1056/NEJMoa1709030. Epub 2017 Sep 10.