TriangleNCT02388906 · CITED IN SOURCE DOCUMENTS
Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-04-24
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Recurrence-free Survival (RFS)
Overall Survival (OS)
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events
the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities
Recurrence-free Survival by PD-L1 Expression
Health Related Quality of Life (HRQoL) Evaluation
Recurrence-free Survival (RFS)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 15 Years
- sex
- ALL
- std Ages
- CHILD
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: Ipilimumab
- Other: Placebo matching Nivolumab
- label
- Ipilimumab and Placebo matching Nivolumab
- type
- EXPERIMENTAL
- intervention Names
- Drug: Nivolumab
- Other: Placebo matching Ipilimumab
- label
- Nivolumab and Placebo matching Ipilimumab
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Ipilimumab and Placebo matching Nivolumab
- description
- Specified dose on specified days
- name
- Ipilimumab
- type
- DRUG
- arm Group Labels
- Nivolumab and Placebo matching Ipilimumab
- description
- Specified dose on specified days
- name
- Nivolumab
- type
- DRUG
- arm Group Labels
- Nivolumab and Placebo matching Ipilimumab
- description
- Specified dose on specified days
- name
- Placebo matching Ipilimumab
- type
- OTHER
- arm Group Labels
- Ipilimumab and Placebo matching Nivolumab
- description
- Specified dose on specified days
- name
- Placebo matching Nivolumab
- type
- OTHER
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 906
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.
- measure
- Recurrence-free Survival (RFS)
- time Frame
- up to 36 months
- secondary Outcomes
- description
- OS is defined as as the time between the date of randomization and the date of death.
- measure
- Overall Survival (OS)
- time Frame
- up to 106.6 months
- description
- the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events
- measure
- The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
- time Frame
- reported between first dose and 30 days after last dose of study therapy
- description
- The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events
- measure
- The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events
- time Frame
- reported between the first dose and 30 days after last dose of study therapy
- description
- the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of Deaths
- measure
- the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths
- time Frame
- reported between first dose and 30 to 100 days after last dose of study therapy
- description
- The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities.
- measure
- The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities
- time Frame
- reported after first dose and within 30 days of last dose of the study therapy
- description
- Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression)
- measure
- Recurrence-free Survival by PD-L1 Expression
- time Frame
- up to 106.6 months
- description
- HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 global health status/QoL composite scale and in remaining EORTC QLQ-C30 scales in all randomized participants. EORTC QLQ-C30 is the most commonly used QoL instrument in melanoma clinical studies, is a 30-item instrument that has gained wide acceptance in oncology clinical studies and comprises 5 functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Except for the overall health status and global quality of life items, responses for all items are 4 point categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health status/quality of life responses are 7-point Likert scales for which higher score reflects higher health status/quality of life for the 7-point Likert scale.
- measure
- Health Related Quality of Life (HRQoL) Evaluation
- time Frame
- up to 36 months
Full study description
- brief Summary
- The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
Source references
- references
- citation
- 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. 2026 Jan 22;394(4):333-342. doi: 10.1056/NEJMoa2504966. Epub 2025 Oct 18.
- pmid
- 41124198
- type
- DERIVED
- citation
- 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.
- pmid
- 39378385
- type
- DERIVED
- citation
- 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.
- pmid
- 39102624
- type
- DERIVED
- 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.
- pmid
- 35964471
- type
- DERIVED
- 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.
- pmid
- 34663559
- type
- DERIVED
- 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.
- pmid
- 34452930
- type
- DERIVED
- 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.
- pmid
- 32961119
- type
- DERIVED
- 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.
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- ratio c (95% CI) p-value d 0.42 (0.30, 0.59) p<0.0001 Figure 4: Recurrence-free Survival - CHECKMATE-76K opdivo-rfs-checkmate-76k CHECKMATE-238 CHECKMATE-238 (NCT02388906) was a randomized, double-blind trial in 906 patients with completely resected Stage IIIB/C or Stage IV melanoma. Patients were randomized (1:1) to receive OPD
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- ="-1">Evidence (nivolumab):</p> <div class="pdq-content-list"><ol id="_1105"><li> In a multinational double-blind trial (<a href="/clinicaltrials/NCT02388906">CheckMate 238</a> [NCT02388906]), patients with stage IIIB, IIIC, or IV melanoma who underwent complete resection were randomly assigned (1:1) to receive eith
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Preserved source evidence · Not medical advice