Clinical trial NCT00636168: Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma
Official title: Adjuvant Immunotherapy With Anti-CTLA-4 Monoclonal Antibody (Ipilimumab) Versus Placebo After Complete Resection of High Risk Stage III Melanoma: A Randomized, Double-blind Phase 3 Trial of the EORTC Melanoma Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: High Risk Stage III Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-03-14
Enrollment: 1211
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 purpose of the study is to determine if ipilimumab is effective in preventing or delaying recurrence and prolongs survival after complete resection of high risk stage III melanoma


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

Inclusion Criteria:

* Age ≥ 18 years
* Complete and adequate resection of Stage III melanoma with histologically confirmed melanoma metastatic to lymph node
* Disease-free
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* Randomization within 12 weeks of surgery

Exclusion Criteria:

* Prior therapy for melanoma except surgery
* Auto-immune disease

Primary outcomes:
measure: Recurrence Free Survival (RFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
timeFrame: Date of randomization to first date of recurrence or death or last available disease assessment with RFS data up to 5 years. Median follow-up was 2.7 years.
measure: Number of Participants With Recurrence or Death as Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
timeFrame: Date of randomization to first date of recurrence or death or last available disease assessment with RFS data upto 5 years. Median follow-up was 2.7 years.
measure: Recurrence-Free Survival (RFS) Rates Per IRC at 1 Year, 2 Years, and 3 Years in the ITT Population
timeFrame: At years 1, 2, and 3
Secondary outcomes:
measure: Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
timeFrame: From June 2008 to January 2016 (approximately 90 months)
measure: Number of Participants With Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
timeFrame: From June 2008 to January 2016 (approximately 90 months)
measure: Distant Metastasis-Free Survival (DMFS) Rates Per IRC at 1 Year, 2 Years, 3 Years, 4 Years and 5 Years in the ITT Population
timeFrame: At years 1, 2, 3, 4 and 5
measure: Overall Survival in the Intent to Treat (ITT) Population
timeFrame: From June 2008 to January 2016 (approximately 90 months)
measure: Rate of Overall Survival (OS)
timeFrame: From date of randomization to date of death, assessed up to 9 years
measure: Number of Participants With On-Study Adverse Events (AEs) Leading to Discontinuation of Treatment, Serious AEs (SAEs), Drug-Related SAEs, Immune-related AEs (irAEs), Immune-mediated Adverse Reactions (imARs), Deaths in Treated Population
timeFrame: Day 1 up to 70 days after last dose; up to 5 years
measure: Number of Participants With Serious Adverse Events (SAEs), Non-serious AEs (NSAEs) and Number of Deaths: Overall Study
timeFrame: SAEs and NSAEs: Day 1 up to 70 days after last dose(safety window). Deaths: All deaths regardless of 70 day safety window.Up to 10 years
measure: Exposure Adjusted Incidence Rate of Adverse Events Including Multiple Occurrences of Unique Events
timeFrame: Day 1 up to 70 days after last dose; up to 5 years
measure: Mean Change From Baseline in Global Health Status Scores at Each Assessment Timepoint
timeFrame: Baseline up to 2 years from randomization
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: North. Cal. Melanoma Center-St. Mary's Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Boca Raton
country: United States
facility: Boca Raton Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Cnt And Res Inst
state: Florida
city: Park Ridge
country: United States
facility: Oncology Specialists, S.C.
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Center
state: Nevada
city: Morristown
country: United States
facility: Atlantic Melanoma Center
state: New Jersey
city: Albuquerque
country: United States
facility: University Of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Bethlehem
country: United States
facility: St Lukes Hospital And Health Network
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Ctr
state: Tennessee
city: Dallas
country: United States
facility: Center For Oncology Research & Treatment, P.A.
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute At The Univ. Of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Waratah
country: Australia
facility: Local Institution
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution
state: Queensland
city: Woolloongabba
country: Australia
facility: Local Institution
state: Queensland
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution
state: Western Australia
city: Graz
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Praha 2
country: Czechia
facility: Local Institution
city: Praha 2
country: Czechia
facility: Local Institution
city: Aarhus C
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense C
country: Denmark
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Turku
country: Finland
facility: Local Institution
city: Lillie
country: France
facility: Local Institution
state: Cedex
city: Boulogne-billancourt
country: France
facility: Local Institution
city: Marseille Cedex 5
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pierre Benite
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
city: Villejuif
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Gottingen
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Kiel
country: Germany
facility: Local Institution
city: Koln
country: Germany
facility: Local Institution
city: Luebeck
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Tubingen
country: Germany
facility: Local Institution
city: Wurzburg
country: Germany
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Leiden
country: Netherlands
facility: Local Institution
city: Nijmegen
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Oslo
country: Norway
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Pyatigorsk
country: Russian Federation
facility: Local Institution
state: Stavropol Region
city: Ivanovo
country: Russian Federation
facility: Local Institution
city: Izhevsk
country: Russian Federation
facility: Local Institution
city: Krasnodar
country: Russian Federation
facility: Local Institution
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution
city: Lipetsk
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Petrozavodsk
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Tomsk
country: Russian Federation
facility: Local Institution
city: Ufa
country: Russian Federation
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Zaragoza
country: Spain
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Zurich
country: Switzerland
facility: Local Institution
city: Chelmsford
country: United Kingdom
facility: Local Institution
state: Essex
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Southampton
country: United Kingdom
facility: Local Institution
state: Hampshire
city: Nottingham
country: United Kingdom
facility: Local Institution
state: Nottinghamshire
city: Leeds
country: United Kingdom
facility: Local Institution
state: Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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: Coens C, Suciu S, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bottomley A, Kotapati S, de Pril V, Testori A, Eggermont AMM. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial. Lancet Oncol. 2017 Mar;18(3):393-403. doi: 10.1016/S1470-2045(17)30015-3. Epub 2017 Feb 3.
citation: Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med. 2016 Nov 10;375(19):1845-1855. doi: 10.1056/NEJMoa1611299. Epub 2016 Oct 7.
citation: Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Konto C, Hoos A, de Pril V, Gurunath RK, de Schaetzen G, Suciu S, Testori A. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 May;16(5):522-30. doi: 10.1016/S1470-2045(15)70122-1. Epub 2015 Mar 31.