Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma

NCT ID: NCT02388906

Last Updated: 2025-04-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

906 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-16

Study Completion Date

2024-10-16

Brief Summary

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

Detailed Description

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Conditions

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Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ipilimumab and Placebo matching Nivolumab

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type DRUG

Specified dose on specified days

Placebo matching Nivolumab

Intervention Type OTHER

Specified dose on specified days

Nivolumab and Placebo matching Ipilimumab

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Specified dose on specified days

Placebo matching Ipilimumab

Intervention Type OTHER

Specified dose on specified days

Interventions

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Ipilimumab

Specified dose on specified days

Intervention Type DRUG

Nivolumab

Specified dose on specified days

Intervention Type DRUG

Placebo matching Ipilimumab

Specified dose on specified days

Intervention Type OTHER

Placebo matching Nivolumab

Specified dose on specified days

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0036

Little Rock, Arkansas, United States

Site Status

Local Institution - 0117

La Jolla, California, United States

Site Status

Local Institution - 0189

Los Angeles, California, United States

Site Status

Local Institution - 0021

San Francisco, California, United States

Site Status

Local Institution - 0006

San Francisco, California, United States

Site Status

Local Institution - 0010

Aurora, Colorado, United States

Site Status

Local Institution - 0004

Washington D.C., District of Columbia, United States

Site Status

Local Institution - 0012

Jacksonville, Florida, United States

Site Status

Local Institution - 0019

Miami Beach, Florida, United States

Site Status

Local Institution - 0030

Orlando, Florida, United States

Site Status

Local Institution - 0032

Tampa, Florida, United States

Site Status

Local Institution - 0016

Atlanta, Georgia, United States

Site Status

Local Institution - 0106

Chicago, Illinois, United States

Site Status

Local Institution - 0013

Boston, Massachusetts, United States

Site Status

Local Institution - 0170

Boston, Massachusetts, United States

Site Status

Local Institution - 0171

Boston, Massachusetts, United States

Site Status

Local Institution - 0015

Ann Arbor, Michigan, United States

Site Status

Local Institution - 0002

Robbinsdale, Minnesota, United States

Site Status

Local Institution - 0017

St Louis, Missouri, United States

Site Status

Local Institution - 0123

Hackensack, New Jersey, United States

Site Status

Local Institution - 0095

New Brunswick, New Jersey, United States

Site Status

Local Institution - 0024

New York, New York, United States

Site Status

Local Institution - 0033

New York, New York, United States

Site Status

Local Institution - 0003

Charlotte, North Carolina, United States

Site Status

Local Institution - 0025

Durham, North Carolina, United States

Site Status

Local Institution - 0157

Columbus, Ohio, United States

Site Status

Local Institution - 0031

Portland, Oregon, United States

Site Status

Local Institution - 0029

Portland, Oregon, United States

Site Status

Local Institution - 0022

Allentown, Pennsylvania, United States

Site Status

Local Institution - 0001

Bethlehem, Pennsylvania, United States

Site Status

Local Institution - 0026

Charleston, South Carolina, United States

Site Status

Local Institution - 0014

Nashville, Tennessee, United States

Site Status

Local Institution - 0005

Dallas, Texas, United States

Site Status

Local Institution - 0027

Charlottesville, Virginia, United States

Site Status

Local Institution - 0126

Seattle, Washington, United States

Site Status

Local Institution - 0142

Capital Federal, Buenos Aires, Argentina

Site Status

Local Institution - 0140

San Miguel de Tucumán, Tucumán Province, Argentina

Site Status

Local Institution

Córdoba, , Argentina

Site Status

Local Institution - 0079

Gateshead, New South Wales, Australia

Site Status

Local Institution - 0080

Westmead, New South Wales, Australia

Site Status

Local Institution - 0078

Wollstonecraft, New South Wales, Australia

Site Status

Local Institution - 0082

Greenslopes, Queensland, Australia

Site Status

Local Institution - 0083

Southport, Queensland, Australia

Site Status

Local Institution - 0084

Adelaide, South Australia, Australia

Site Status

Local Institution - 0075

Heidelberg, Victoria, Australia

Site Status

Local Institution - 0077

Prahran, Victoria, Australia

Site Status

Local Institution - 0085

Nedlands, Western Australia, Australia

Site Status

Local Institution - 0081

Camperdown, , Australia

Site Status

Local Institution - 0169

Graz, , Austria

Site Status

Local Institution - 0168

Salzburg, , Austria

Site Status

Local Institution - 0038

Brussels, , Belgium

Site Status

Local Institution - 0040

Brussels, , Belgium

Site Status

Local Institution - 0037

Ghent, , Belgium

Site Status

Local Institution - 0039

Leuven, , Belgium

Site Status

Local Institution - 0051

Edmonton, Alberta, Canada

Site Status

Local Institution - 0074

Vancouver, British Columbia, Canada

Site Status

Local Institution - 0094

Toronto, Ontario, Canada

Site Status

Local Institution - 0105

Montreal, Quebec, Canada

Site Status

Local Institution - 0046

Québec, Quebec, Canada

Site Status

Local Institution - 0101

Hradec Králové, , Czechia

Site Status

Local Institution - 0102

Ostrava-Poruba, , Czechia

Site Status

Local Institution - 0099

Prague, , Czechia

Site Status

Local Institution - 0100

Prague, , Czechia

Site Status

Local Institution - 0047

Helsinki, , Finland

Site Status

Local Institution - 0048

Tampere, , Finland

Site Status

Local Institution - 0138

Lille, , France

Site Status

Local Institution - 0135

Marseille, , France

Site Status

Local Institution - 0134

Nantes, , France

Site Status

Local Institution - 0136

Paris, , France

Site Status

Local Institution - 0133

Pierre-Bénite, , France

Site Status

Local Institution - 0137

Toulouse, , France

Site Status

Local Institution - 0086

Athens, , Greece

Site Status

Local Institution - 0087

Neo Faliro, , Greece

Site Status

Local Institution - 0163

Budapest, , Hungary

Site Status

Local Institution - 0063

Dublin, , Ireland

Site Status

Local Institution - 0166

Dublin, , Ireland

Site Status

Local Institution - 0108

Dublin, , Ireland

Site Status

Local Institution - 0064

Galway, , Ireland

Site Status

Local Institution - 0112

Bergamo, , Italy

Site Status

Local Institution - 0116

Genova, , Italy

Site Status

Local Institution - 0115

Meldola (FC), , Italy

Site Status

Local Institution - 0113

Milan, , Italy

Site Status

Local Institution - 0107

Napoli, , Italy

Site Status

Local Institution - 0111

Padua, , Italy

Site Status

Local Institution - 0114

Roma, , Italy

Site Status

Local Institution - 0110

Siena, , Italy

Site Status

Local Institution - 0179

Nagoya, Aichi-ken, Japan

Site Status

Local Institution - 0161

Fukuoka, Fukuoka, Japan

Site Status

Local Institution - 0174

Tsukuba, Ibaraki, Japan

Site Status

Local Institution - 0162

Kumamoto, Kumamoto, Japan

Site Status

Local Institution - 0160

Matsumoto, Nagano, Japan

Site Status

Local Institution - 0175

Niigata, Niigata, Japan

Site Status

Local Institution - 0176

Osaka, Osaka, Japan

Site Status

Local Institution - 0159

Sunto-gun, Shizuoka, Japan

Site Status

Local Institution - 0158

Chuo-ku, Tokyo, Japan

Site Status

Local Institution - 0180

Chuo-shi, Yamanashi, Japan

Site Status

Local Institution - 0042

Amsterdam, , Netherlands

Site Status

Local Institution - 0045

Groningen, , Netherlands

Site Status

Local Institution - 0043

Nijmegen, , Netherlands

Site Status

Local Institution - 0041

Veldhoven, , Netherlands

Site Status

Local Institution - 0098

Bergen, , Norway

Site Status

Local Institution - 0109

Oslo, , Norway

Site Status

Local Institution - 0150

Gdansk, , Poland

Site Status

Local Institution - 0149

Krakow, , Poland

Site Status

Local Institution - 0152

Warsaw, , Poland

Site Status

Local Institution - 0156

Craiova, , Romania

Site Status

Local Institution - 0153

Romania, , Romania

Site Status

Local Institution - 0148

Johannesburg, Gauteng, South Africa

Site Status

Local Institution - 0145

Pretoria, Gauteng, South Africa

Site Status

Local Institution - 0147

Saxonwold, Johannesburg, Gauteng, South Africa

Site Status

Local Institution - 0181

Cape Town, Western Cape, South Africa

Site Status

Local Institution - 0146

Kraaifontein, Western Cape, South Africa

Site Status

Local Institution - 0144

Songpa-gu, Seoul, South Korea

Site Status

Local Institution - 0129

Seoul, , South Korea

Site Status

Local Institution - 0127

Seoul, , South Korea

Site Status

Local Institution - 0128

Seoul, , South Korea

Site Status

Local Institution - 0120

Barcelona, , Spain

Site Status

Local Institution - 0119

Madrid, , Spain

Site Status

Local Institution - 0121

Seville, , Spain

Site Status

Local Institution - 0122

Valencia, , Spain

Site Status

Local Institution - 0050

Gothenberg, , Sweden

Site Status

Local Institution - 0096

Lund, , Sweden

Site Status

Local Institution - 0167

Zurich, , Switzerland

Site Status

Local Institution - 0131

Kaohsiung City, , Taiwan

Site Status

Local Institution - 0132

Taichung, , Taiwan

Site Status

Local Institution - 0130

Taoyuan District, , Taiwan

Site Status

Local Institution - 0057

Bristol, Avon, United Kingdom

Site Status

Local Institution - 0052

Swansea, Carmarthenshire, United Kingdom

Site Status

Local Institution - 0165

London, Greater London, United Kingdom

Site Status

Local Institution - 0054

Manchester, Greater Manchester, United Kingdom

Site Status

Local Institution - 0056

Southampton, Hampshire, United Kingdom

Site Status

Local Institution - 0177

Northwood, Middlesex, United Kingdom

Site Status

Local Institution - 0055

Oxford, Oxfordshire, United Kingdom

Site Status

Local Institution - 0060

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Site Status

Local Institution - 0097

Leicester, , United Kingdom

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Local Institution - 0053

Surrey, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Canada Czechia Finland France Greece Hungary Ireland Italy Japan Netherlands Norway Poland Romania South Africa South Korea Spain Sweden Switzerland Taiwan United Kingdom

References

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Ascierto PA, Del Vecchio M, Merelli B, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Gaudy-Marqueste C, Pigozzo J, Marquez-Rodas I, Butler MO, Di Giacomo AM, Gligich O, De La Cruz-Merino L, Arenberger P, Atkinson V, Nathan P, Hill A, Millward M, Fecher LA, Khushalani NI, Queirolo P, Soomro R, Rathod D, Askelson M, Pe Benito M, Joseph D, Larkin J. Nivolumab for Resected Stage III or IV Melanoma at 9 Years. N Engl J Med. 2025 Oct 18. doi: 10.1056/NEJMoa2504966. Online ahead of print.

Reference Type DERIVED
PMID: 41124198 (View on PubMed)

Weber JS, Middleton MR, Yates G, Sharpe DJ, Kurt M, Lobo M, Moshyk A, Vanderpuye-Orgle J, Mohr P. Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials. J Clin Oncol. 2025 Mar 10;43(8):929-937. doi: 10.1200/JCO.24.00237. Epub 2024 Oct 8.

Reference Type DERIVED
PMID: 39378385 (View on PubMed)

Weber J, 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, Di Giacomo AM, 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, Larkin J. Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238. J Clin Oncol. 2024 Nov;42(31):3702-3712. doi: 10.1200/JCO.23.01448. Epub 2024 Aug 5.

Reference Type DERIVED
PMID: 39102624 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35964471 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34663559 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34452930 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32961119 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28891423 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2014-002351-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-238

Identifier Type: -

Identifier Source: org_study_id

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