An Investigational Immuno-therapy Study of Nivolumab Combined With Ipilimumab Compared to Nivolumab by Itself After Complete Surgical Removal of Stage IIIb/c/d or Stage IV Melanoma
- Conditions
- Melanoma
- Interventions
- Biological: nivolumabBiological: ipilimumab
- Registration Number
- NCT03068455
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether an investigational immunotherapy Nivolumab, when combined with Ipilimumab, is more effective than Nivolumab by itself, in delaying the return of cancer in patients who have had a complete surgical removal of stage IIIb/c/d or stage IV Melanoma
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1844
- Completely surgically resected stage IIIb/c/d or stage IV melanoma within 12 weeks of participation in study.
- Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work
- No prior anti-cancer treatment for melanoma (except surgery for the melanoma lesion(s) and/or except for adjuvant radiation therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions)
- History of uveal melanoma
- Patients with active, known or suspected autoimmune disease
- Prior treatment with interferon (if complete < 6 months prior to participation in study), anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Other protocol defined inclusion/exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description nivolumab + ipilimumab ipilimumab Specified Dose on Specified Days nivolumab nivolumab Specified Dose on Specified Days nivolumab + ipilimumab nivolumab Specified Dose on Specified Days
- Primary Outcome Measures
Name Time Method Recurrence-free Survival (RFS) - All Randomized Participants With PD-L1 Expression Level < 1% From randomization to Primary Completion Date (up to approximately 3 years) RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.
Median based on Kaplan-Meier Estimates.Recurrence-free Survival (RFS) - All Randomized Participants From randomization to Primary Completion Date (up to approximately 3 years) RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.
Median values based on Kaplan-Meier Estimates.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) - All Randomized Participants From randomization to date of death (up to approximately 45 months) OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.
Overall Survival (OS) - All Randomized Participants With PD-L1 Expression Level < 1% From randomization to date of death (up to approximately 45 months) OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.
Time From Next Therapy to Second Next Therapy - All Randomized Participants With PD-L1 Expression Level < 1% From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months) Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.
Time to Next-Line Therapies - All Randomized Participants From randomization to start of next therapy or second next therapy (up to approximately 45 months) Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date.
Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date.Time From Next Therapy to Second Next Therapy - All Randomized Participants From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months) Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.
Time to Next-Line Therapies - All Randomized Participants With PD-L1 Expression Level < 1% From randomization to start of next therapy or second next therapy (up to approximately 45 months) Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date.
Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive dateProgression-free Survival (PFS) on Next-line Therapy - All Randomized Participants From randomization to progression event (up to approximately 45 months) PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression From randomization to Study Completion Date (up to approximately 45 months) RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.
Median based on Kaplan-Meier Estimates.Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants With PD-L1 Expression Level < 1% From randomization to progression event (up to approximately 45 months) PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.
Trial Locations
- Locations (70)
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Istituto Nazionale Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Istituto Oncologico Veneto IOV
🇮🇹Padova, Italy
Carolinas Med Ctr
🇺🇸Charlotte, North Carolina, United States
Hospital Regional Universitario De Malaga
🇪🇸Malaga, Spain
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Memorial Sloan Kettering Nassau
🇺🇸New York, New York, United States
Christie Hospital Nhs Trust
🇬🇧Manchester, United Kingdom
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University Of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
CHU de Quebec - Universite Laval
🇨🇦Quebec, Canada
Royal Marsden Hospital - Surrey
🇬🇧Sutton., United Kingdom
Institut Gustave Roussy
🇫🇷Villejuif, France
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
St. Luke's University Health Network
🇺🇸Easton, Pennsylvania, United States
Local Institution
🇬🇧Oxford, Oxfordshire, United Kingdom
Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Dermatovenerologicka klinika 3. LF UK a FNKV
🇨🇿Praha 10, Czechia
Hospital Universitari Germans Trias I Pujol
🇪🇸Badalona-barcelona, Spain
Chu Nantes
🇫🇷Nantes, France
Klinika Nowotworow Ukladowych i Uogolnionych
🇵🇱Krakow, Poland
ASST Papa Giovanni XXIII
🇮🇹Bergamo, Italy
IRCCS Istituto Nazionale Tumori Milano
🇮🇹Milano, Italy
Hopital Saint Louis
🇫🇷Paris, France
Hopital Claude Huriez
🇫🇷LILLE Cedex, France
Hospital Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Institut Claudius Regaud
🇫🇷Toulouse Cedex 9, France
Hosp Univ Virgen Macarena
🇪🇸Sevilla, Spain
H. Univ. Vall dHebron
🇪🇸Barcelona, Spain
Klinika onkologie a radioterapie
🇨🇿Hradec Kralove, Czechia
Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
🇵🇱Warszawa, Poland
Institute Of Oncology "Prof.Dr.Alexandru Trestioreanu" Bucha
🇷🇴Bucharest, Romania
Sf. Nectarie Oncology Center
🇷🇴Craiova, Romania
Dermatovenerologicka klinika VFN a 1. LF UK
🇨🇿Praha 2, Czechia
Hopital De La Timone
🇫🇷Marseille Cedex 5, France
The Beatson West Of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Klinika komplexni onkologicke pece
🇨🇿Brno, Czechia
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite Cedex, France
Centre Hospitalier Universitaire Dijon Bocage
🇫🇷Dijon, France
Laiko Hospital
🇬🇷Athens, Greece
Metropolitan Hospital
🇬🇷Athens, Greece
The Angeles Clinic & Research Institute
🇺🇸Los Angeles, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Oncology Specialists, S.C.
🇺🇸Park Ridge, Illinois, United States
Mass General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Inova Melanoma and Skin Cancer Center
🇺🇸Fairfax, Virginia, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University Of Washington Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Md Anderson Can Cnt
🇺🇸Houston, Texas, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Georgetown University Med Ctr
🇺🇸Washington, District of Columbia, United States
University Of Chicago
🇺🇸Chicago, Illinois, United States
Texas Oncology Sammons Cancer Center
🇺🇸Dallas, Texas, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University Of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Providence Cancer Center Oncology And Hematology Care
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The Royal Marsden Hospital
🇬🇧London, United Kingdom