Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma

Melanoma Clinical Trial

— CheckMate76K  

Official title:

A Phase 3, Randomized, Double-Blind Study of Adjuvant Immunotherapy With Nivolumab Versus Placebo After Complete Resection of Stage IIB/C Melanoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04099251
• Other study ID #: CA209-76K
• Secondary ID: 2019-001230-34U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 28, 2019
• Est. completion date: June 29, 2027

Study information

• Verified date: November 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effectiveness of nivolumab adjuvant immunotherapy compared to placebo in adults and pediatric participants after complete resection of Stage IIB/C melanoma with no evidence of disease (NED) who are at high risk for recurrence.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 790
• Est. completion date: June 29, 2027
• Est. primary completion date: June 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Had a negative sentinel lymph node biopsy
• Participant has not been previously treated for melanoma
• ECOG 0 or 1
• Participants must have been diagnosed with histologically confirmed, Resected, Stage IIB/C cutaneous melanoma

Exclusion Criteria:

• History of ocular or mucosal melanoma.
• Pregnant or nursing women
• Participants with active known or suspected autoimmune disease
• Known history of allergy or hypersensitivity to study drug components
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or agents that target IL-2 pathways, T-cell stimulators, or checkpoint pathways Other protocol defined inclusion/exclusion criteria apply.

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• Nivolumab
Specified dose on specified days

Other:
• Placebo
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution - 0019	Box Hill	Victoria
Australia	Local Institution - 0105	Cairns	Queensland
Australia	Local Institution - 0125	Geelong	Victoria
Australia	Local Institution - 0017	Greenslopes	Queensland
Australia	Local Institution - 0024	Herston	Queensland
Australia	Local Institution - 0128	Malvern	Victoria
Australia	Local Institution - 0106	Melbourne	Victoria
Australia	Local Institution - 0104	Nedlands	Western Australia
Australia	Local Institution - 0138	Southport	Queensland
Australia	Local Institution - 0018	Waratah	New South Wales
Australia	Local Institution - 0025	Westmead	New South Wales
Australia	Local Institution - 0016	Wollstonecraft	New South Wales
Austria	Local Institution - 0049	Graz
Austria	Local Institution - 0051	Innsbruck
Austria	Local Institution - 0050	Salzburg
Austria	Local Institution - 0048	Wien
Belgium	Local Institution - 0028	Charleroi
Belgium	Local Institution - 0011	Gent
Belgium	Local Institution - 0008	Kortrijk
Belgium	Local Institution - 0010	Liège
Canada	Local Institution - 0134	Calgary	Alberta
Canada	Local Institution - 0131	Halifax	Nova Scotia
Canada	Local Institution - 0142	Hamilton	Ontario
Canada	Local Institution - 0124	Kingston	Ontario
Canada	Local Institution - 0116	Montreal	Quebec
Canada	Local Institution - 0123	Sherbrooke	Quebec
Canada	Local Institution - 0140	Toronto	Ontario
Canada	Local Institution - 0133	Vancouver	British Columbia
Czechia	Local Institution - 0075	Ostrava-Poruba
Czechia	Local Institution - 0074	Prague	Praha 2
Czechia	Local Institution - 0073	Praha 10
Denmark	Local Institution - 0007	Aarhus N
Denmark	Local Institution - 0012	Herlev
Denmark	Local Institution - 0013	Odense
Finland	Local Institution - 0014	Helsinki	Etelä-Suomen Lääni
Finland	Local Institution - 0015	Tampere	Pirkanmaa
Finland	Local Institution - 0110	Turku
France	Local Institution - 0129	Besancon Cedex
France	Local Institution - 0112	Bordeaux
France	Local Institution - 0113	Brest	Finistère
France	Local Institution - 0111	Lille
France	Local Institution - 0033	Marseille
France	Local Institution - 0035	Nantes
France	Local Institution - 0130	Nice
France	Local Institution - 0036	Paris
France	Local Institution - 0032	Pierre Benite Cedex
France	Local Institution - 0034	Villejuif
Germany	Local Institution - 0072	Bonn
Germany	Local Institution - 0061	Buxtehude
Germany	Local Institution - 0098	Dresden
Germany	Local Institution - 0054	Essen
Germany	Local Institution - 0062	Gera
Germany	Local Institution - 0114	Goettingen
Germany	Local Institution - 0060	Hannover
Germany	Local Institution - 0055	Heidelberg
Germany	Local Institution - 0057	Lubeck
Germany	Local Institution - 0100	Mainz
Germany	Local Institution - 0056	München	Bayern
Germany	Local Institution - 0102	Regensburg
Germany	Local Institution - 0058	Tuebingen
Greece	Local Institution - 0082	Athina
Greece	Local Institution - 0084	Piraeus
Greece	Local Institution - 0083	Thessaloniki
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	IRCCS Istituto Nazionale Tumori Milano	Milano
Italy	Istituto Europeo di Oncologia IRCCS	Milano
Italy	Istituto Nazionale Tumori Fondazione Pascale	Napoli
Italy	Istituto Oncologico Veneto IOV	Padova
Italy	A.O.U. Policlinico Paolo Giaccone	Palermo	Sicilia
Italy	Azienda Ospedaliera Di Perugia	Perugia
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Netherlands	Local Institution - 0107	Breda
Netherlands	Local Institution - 0001	Groningen
Netherlands	Local Institution - 0030	Rotterdam
Netherlands	Local Institution - 0002	Utrecht
Norway	Local Institution - 0063	Bergen
Norway	Local Institution - 0027	Gralum
Norway	Local Institution - 0005	Oslo
Poland	Local Institution - 0023	Gdansk
Poland	Local Institution - 0103	Poznan	Wielkopolskie
Poland	Local Institution - 0022	Warszawa
Romania	Local Institution - 0047	Cluj-Napoca
Romania	Local Institution - 0020	Craiova
Romania	Local Institution - 0021	Sector 2
Spain	Local Institution - 0067	A Coruña
Spain	Local Institution - 0065	Badalona
Spain	Local Institution - 0071	Barcelona
Spain	Local Institution - 0066	Madrid
Spain	Local Institution - 0070	Madrid
Spain	Local Institution - 0068	Malaga
Spain	Local Institution - 0064	Santander
Spain	Local Institution - 0069	Valencia
Sweden	Local Institution - 0003	Linköping	Östergötlands Län [se-05]
Sweden	Local Institution - 0026	Orebro
Switzerland	Local Institution - 0053	Lausanne
Switzerland	Local Institution - 0052	Zuerich
United Kingdom	Local Institution - 0044	Cardiff
United Kingdom	Local Institution - 0095	Southampton
United States	Local Institution - 0092	Allentown	Pennsylvania
United States	Local Institution - 0141	Atlanta	Georgia
United States	Local Institution - 0091	Aurora	Colorado
United States	Local Institution - 0144	Austin	Texas
United States	Local Institution - 0135	Baltimore	Maryland
United States	Local Institution - 0088	Birmingham	Alabama
United States	Local Institution - 0078	Boston	Massachusetts
United States	Local Institution - 0127	Boston	Massachusetts
United States	Local Institution - 0143	Boston	Massachusetts
United States	Local Institution - 0086	Charlotte	North Carolina
United States	Local Institution - 0132	Chicago	Illinois
United States	Local Institution - 0099	Cleveland	Ohio
United States	Local Institution - 0085	Dallas	Texas
United States	Local Institution - 0090	Fairfax	Virginia
United States	Local Institution - 0148	Germantown	Tennessee
United States	Local Institution - 0093	Hackensack	New Jersey
United States	Local Institution - 0080	Los Angeles	California
United States	Local Institution - 0094	New York	New York
United States	Local Institution - 0079	Omaha	Nebraska
United States	Local Institution - 0031	Pittsburgh	Pennsylvania
United States	Local Institution - 0076	Portland	Oregon
United States	Local Institution - 0081	Robbinsdale	Minnesota
United States	Local Institution - 0077	San Francisco	California
United States	Local Institution - 0119	San Francisco	California
United States	Local Institution - 0122	San Jose	California
United States	Local Institution - 0087	Springdale	Arkansas
United States	Local Institution - 0126	Tucson	Arizona
United States	Local Institution - 0109	Vallejo	California
United States	Local Institution - 0120	Vallejo	California
United States	Local Institution - 0121	Vallejo	California
United States	Local Institution - 0089	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Netherlands,  Norway,  Poland,  Romania,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Survival (RFS)	Recurrence Free Survival (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 (including melanoma in situ), or death (whatever the cause), whichever occurs first. For participants who remain alive and whose disease has not recurred or did not die, RFS will be censored on the date of last evaluable disease assessment. For those participants who remained alive and had no recorded post-randomization tumor assessment, RFS will be censored on the day of randomization.	From randomization up to the date of first recurrence, new primary melanoma, or death (whatever the cause), whichever occurs first (up to 32 months)
Secondary	Distant Metastasis-Free Survival (DMFS)	Investigator-assessed distant metastasis-free survival (DMFS) is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants with no baseline disease assessment, no on-study disease assessments and no death, and no distant metastasis and no death will be censored. Participants with no baseline disease assessment and no on-study disease assessments and death are censored on the date of randomization. Participants with no recurrence and no death will be censored on the date of their last evaluable disease assessment.	From randomization up to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first (up to approximately 32 months)
Secondary	Duration of Treatment on Next Line Therapy Per Investigator Assessment	Duration of treatment is an investigator-assessed outcome of next-line therapy (NLT) defined as the time from first dose date of NLT to last dose date of NLT. Participants who did not stop the NLT were censored.	From first dose date of next-line therapy to last dose date of next-line therapy (up to approximately 32 months)
Secondary	Progression-Free Survival Through Next-Line Therapy	Progression-free survival through next-line therapy (PFS2) is defined as the time from randomization to recurrence/objective disease progression after the start of the next-line of systemic anti-cancer therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first. Participants who did not receive subsequent systemic anti-cancer therapy who died will be considered as having the event on the date of death. Participants who received subsequent systemic anti-cancer therapy who had a disease progression after the start of therapy will be considered as having the event on the date of disease progression. Participants who died or started second next-line therapy, the date of death or start date of second next-line therapy will be the event date, whichever is earlier. Participants who did not experience disease progression, death, or second next-line therapy will be censored on the last known alive date.	From randomization to recurrence/objective disease progression after the start of the next-line therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first (up to approximately 32 months)
Secondary	Number of Participants Experiencing Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Adverse Events Leading to Discontinuation	An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Select Adverse Events	The number of participants experiencing all-cause select adverse events (AEs). An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Serious Adverse Events (SAEs)	A Serious Adverse Events (SAE) is defined as any untoward or unfavorable medical occurrence in a participants that results in death, is life threatening, or places the participant at immediate risk of death from the event as it occurred, requires or prolongs hospitalization, causes persistent or significant disability or incapacity, results in congenital anomalies or birth defects, and is another condition which investigators judge to represent significant hazards.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Death	All study participants who died during the blinded phase of the study following treatment.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters	The number of participants experiencing Grade 3 or 4 laboratory abnormalities in the specific pre-determined hematology tests.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters	The number of participants experiencing laboratory abnormalities in the specific pre-determined liver tests.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Secondary	Overall Survival (OS)	OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.	From randomization up to the date of death or the last date the participant was known to be alive

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls