A Study to Evaluate Treatment With Nivolumab Alone and Nivolumab Combined With Ipilimumab in Children With Melanoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to describe real-world safety outcomes in children with melanoma who are treated with nivolumab alone or nivolumab in combination with ipilimumab for unresectable or metastatic melanoma, or treated with adjuvant nivolumab after resection of stage IIB-IV melanoma. Demographic and clinical characteristics, and treatment patterns, will also be described in this population.

Official Title
-----------------
Real-World Evaluation of Patient Characteristics, Treatment Patterns, Safety, and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab for Pediatric Melanoma

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

Intervention / Treatment
-----------------
* Drug: Nivolumab +/- ipilimumab
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with confirmed diagnosis of unresectable or metastatic cutaneous melanoma, or stage IIB-IV cutaneous melanoma who have undergone complete resection Initiated treatment with nivolumab monotherapy or in combination with ipilimumab for unresectable or metastatic melanoma, or as adjuvant therapy for resected stage IIb-IV melanoma, between January 1, 2015 and 6 months prior to data collection For the adjuvant nivolumab cohort, initiated treatment with nivolumab for stage IIb-IV melanoma within 12 weeks following index resection Aged <18 years at the time of nivolumab/ipilimumab treatment initiation At least 6 months of follow-up from index treatment date (unless deceased prior to end of 6 months) Exclusion Criteria: Prior malignancy active within 3 years prior to nivolumab or ipilimumab treatment index date except for locally curable cancers that have been apparently cured (such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast) Receiving nivolumab therapy (monotherapy, combination with ipilimumab, or adjuvant therapy) for melanoma as part of a clinical trial during the study period

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants treated with nivolumab +/- ipilimumab for unresectable/metastatic melanoma<br> | Drug: Nivolumab +/- ipilimumab<br>* Participants treated with nivolumab +/- ipilimumab for unresectable/metastatic melanoma<br>|
| Participants treated with nivolumab as adjuvant therapy for resected stage IIB-IV melanoma<br> | Drug: Nivolumab<br>* Participants treated with nivolumab as adjuvant therapy for resected stage IIB-IV melanoma<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events |  | Up to 100 days after treatment discontinuation | 
| Incidence of all-cause adverse events |  | Up to 100 days after treatment discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant year of birth |  | Six months prior to index date | 
| Participant gender |  | Six months prior to index date | 
| Participant race |  | Six months prior to index date | 
| Participant ethnicity |  | Six months prior to index date | 
| Participant state/region of residence |  | Six months prior to index date | 
| Participant primary insurance payer at treatment initiation |  | Six months prior to index date | 
| Date of initial melanoma diagnosis |  | Six months prior to index date | 
| Date of index resection for participants treated with adjuvant nivolumab |  | Six months prior to index date | 
| Participant height |  | Initiation of index treatment | 
| Participant weight |  | Initiation of index treatment | 
| Stage of melanoma at diagnosis, assessed by American Joint Committee on Cancer criteria |  | Six months prior to index date | 
| Margins at index resection for participants treated with adjuvant nivolumab after resection |  | Six months prior to index date | 
| Lymph node biopsy results |  | Six months prior to index date | 
| Lymph node involvement - Stage III/IV only |  | Six months prior to index date | 
| Tumor ulceration status |  | Six months prior to index date | 
| Tumor ulceration characteristics |  | Six months prior to index date | 
| Eastern Cooperative Oncology Group Performance Status (ECOG-PS) |  | Initiation of index treatment | 
| Lactate dehydrogenase level |  | Initiation of index treatment | 
| Index treatment |  | Initiation of index treatment | 
| Number of lines of therapy received for unresectable/metastatic melanoma |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Number of lines of therapy received post resection |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Disease response characteristics |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Disease recurrence characteristics |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Duration of therapy (DOT) |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Time to next treatment (TTNT) |  | From index therapy initiation to next subsequent systemic melanoma treatment post-nivolumab, death, or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Treatment-free interval (TFI) |  | From discontinuation of index treatment to date of initiation of subsequent therapy, assessed up to 108 months | 
| Overall survival (OS) |  | From index therapy initiation to death or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Healthcare resource utilization assessed by the number of inpatient hospitalizations |  | From initiation of therapy until end of data collection date or death, whichever came first, assessed up to 108 months | 
| Healthcare resource utilization assessed by the number of emergency department (ED) visits |  | From initiation of therapy until end of data collection date or death, whichever came first, assessed up to 108 months | 
| Overall response rate (ORR) in participants with unresectable or metastatic disease | Number of participants with complete or partial response divided by the total number of participants | From index therapy initiation to the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Progression-free survival (PFS) in participants with unresectable or metastatic disease |  | From index therapy initiation to date of first documented disease progression, death, or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Time to initial response (TTR) in participants with unresectable or metastatic disease |  | From index therapy initiation to date of the first physician-reported response (complete or partial response), assessed up to 108 months | 
| Duration of response (DOR) in participants with unresectable or metastatic disease |  | From date of first physician-reported response (complete or partial response) to date of the first physician-reported disease progression, death, or date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Time to progression (TTP) in participants with unresectable or metastatic disease |  | From index therapy initiation to date of physician-reported disease progression, or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Time to local disease recurrence in participants with resected disease |  | From index therapy initiation to date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Recurrence free survival (RFS) in participants with resected disease |  | From index therapy initiation to date of first melanoma recurrence, death, or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Time to distant metastases in participants with resected disease |  | From index therapy initiation to date of last follow/up or study end date, whichever came first, assessed up to 108 months | 
| Distant-metastasis free survival (DMFS) in participants with resected disease |  | From index therapy initiation to date of first distant melanoma metastasis, death, or the date of last follow-up/study end date, whichever came first, assessed up to 108 months | 
| Type of disease recurrence/metastasis in participants with resected disease |  | From index therapy initiation to date of last follow-up visit or study end date, whichever came first, assessed up to 108 months |