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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of 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)

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Drug: Ipilimumab
* Drug: Nivolumab
* Other: Placebo matching Ipilimumab
* Other: Placebo matching Nivolumab


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab and Placebo matching Nivolumab<br> | Drug: Ipilimumab<br>* Specified dose on specified days<br>Other: Placebo matching Nivolumab<br>* Specified dose on specified days<br>|
| Experimental: Nivolumab and Placebo matching Ipilimumab<br> | Drug: Nivolumab<br>* Specified dose on specified days<br>Other: Placebo matching Ipilimumab<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival (RFS) | 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. | up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as as the time between the date of randomization and the date of death. | up to 60 months | 
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events | the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events | reported between first dose and 30 days after last dose of study therapy | 
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events | The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events | reported between the first dose and 30 days after last dose of study therapy | 
| the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths | the safety and tolerability of Nivolumab and Ipilimumab wasmeasured by the incidence of Deaths | reported between first dose and 30 to 100 days after last dose of study therapy | 
| The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities | The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities. | reported after first dose and within 30 days of last dose of the study therapy | 
| Recurrence-free Survival by PD-L1 Expression | Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression) | up to 36 months | 
| Health Related Quality of Life (HRQoL) Evaluation | 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. | up to 36 months |