Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma (CheckMate 238)

• ClinicalTrials.gov Identifier: NCT02388906
• Recruitment Status: Active, not recruiting
• First Posted: March 17, 2015
• Results First Posted: June 15, 2021
• Last Update Posted: January 10, 2024
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: March 10, 2015
• First Posted Date: March 17, 2015
• Results First Submitted Date: April 16, 2021
• Results First Posted Date: June 15, 2021
• Last Update Posted Date: January 10, 2024
• Actual Study Start Date: March 19, 2015
• Actual Primary Completion Date: November 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 11, 2021)

Recurrence-free Survival (RFS) [ Time Frame: up to 36 months ]

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.

• Original Primary Outcome Measures (submitted: March 13, 2015): Recurrence -free-survival [ Time Frame: Upto 36 months ]

Current Secondary Outcome Measures (submitted: June 11, 2021)

• Overall Survival (OS) [ Time Frame: up to 60 months ]
  OS is defined as as the time between the date of randomization and the date of death.
• 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 ]
  the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events
• 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 ]
  The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events
• 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 ]
  the safety and tolerability of Nivolumab and Ipilimumab wasmeasured by the incidence of Deaths
• 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 ]
  The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities.
• Recurrence-free Survival by PD-L1 Expression [ Time Frame: up to 36 months ]
  Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression)
• Health Related Quality of Life (HRQoL) Evaluation [ Time Frame: up to 36 months ]
  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.

• Original Secondary Outcome Measures (submitted: March 13, 2015): Overall survival [ Time Frame: Upto 48 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Brief Summary: The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Drug: Ipilimumab
  Specified dose on specified days
• Drug: Nivolumab
  Specified dose on specified days
• Other: Placebo matching Ipilimumab
  Specified dose on specified days
• Other: Placebo matching Nivolumab
  Specified dose on specified days

Study Arms

• Experimental: Ipilimumab and Placebo matching Nivolumab
  Interventions:

  • Drug: Ipilimumab
  • Other: Placebo matching Nivolumab
• Experimental: Nivolumab and Placebo matching Ipilimumab
  Interventions:

  • Drug: Nivolumab
  • Other: Placebo matching Ipilimumab

Publications *

• 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.
• 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.
• 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. Erratum In: J Immunother Cancer. 2021 Nov;9(11):
• 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. Erratum In: Lancet Oncol. 2021 Oct;22(10):e428.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 22, 2020): 906
• Original Estimated Enrollment (submitted: March 13, 2015): 800
• Estimated Study Completion Date: October 6, 2024
• Actual Primary Completion Date: November 26, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Czechia, Finland, France, Greece, Hungary, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Romania, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Brazil, Czech Republic, Mexico, Turkey

Administrative Information

• NCT Number: NCT02388906
• Other Study ID Numbers: CA209-238; 2014-002351-26 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Ono Pharmaceutical Co. Ltd

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: January 2024