Pembrolizumab in Treating Patients With Advanced Uveal Melanoma
|Stage IIIA Uveal Melanoma Stage IIIB Uveal Melanoma Stage IIIC Uveal Melanoma Stage IV Uveal Melanoma||Biological: Pembrolizumab Other: Laboratory Biomarker Analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Multicenter Phase II Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Patients With Advanced Uveal Melanoma|
- Objective Response Rate (ORR), defined as the percentage of patients achieving a confirmed complete or partial response, as defined by immune-related response criteria (irRC) [ Time Frame: Up to 3 years ]Of note, response rates by RECIST 1.1 criteria will also be assessed although irRC will be used for the primary endpoint. ORR will be stratified by PD-L1 expression and GNAQ/GNA11 mutation status. Differences in ORR between subgroups will be assessed by the Pearson chi-square test.
- Progression-Free Survival (PFS) as defined by RECIST 1.1 criteria [ Time Frame: Time from the first dose of pembrolizumab to progression, assessed up to 3 years ]PFS will be summarized in the method of Kaplan and Meier. Median PFS and PFS at one year will be reported with 95% confidence intervals. PFS analysis based on investigator's assessment using irRC will also be carried out.
- Overall Survival (OS) [ Time Frame: Interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years ]The Kaplan-Meier method will be used to estimate the overall survival. The treatment difference in survival will be assessed by the stratified log-rank test. Median survival and its 95% confidence interval will be estimated and reported.
- Response duration [ Time Frame: Up to 3 years ]If sample size permits, response duration will be summarized descriptively using Kaplan-Meier medians and quartiles. Only the subset of patients who show a complete response or partial response will be included in this analysis.
- Number of Patients With Each Worst‐Grade Toxicity. Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after the last dose of trial treatment ]Count of patients according to the worst‐grade toxicity experienced by each, where worst‐grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life‐threatening; grade 5, death. This endpoint will be reported descriptively without formal statistical analysis.
- Changes in GNAQ/GNA11 mutation status on each patient per institutional protocol [ Time Frame: Baseline up to 2 years ]Differences in PFS and OS between subgroups will be assessed by the stratified logrank test. Differences in ORR between subgroups will be assessed by the Pearson chi-square test. No adjustments will be made for multiple comparisons.
- Change in PD-L1 expression status on archival or fresh tissue from all patients and correlate with ORR [ Time Frame: Baseline up to 2 years ]Differences in PFS and OS between subgroups will be assessed by the stratified logrank test. Differences in ORR between subgroups will be assessed by the Pearson chi-square test. No adjustments will be made for multiple comparisons.
- Changes in molecular characteristics of uveal melanoma when treated with pembrolizumab [ Time Frame: Baseline up to 2 years ]Each relevant clinical characteristic will be recorded by the use of tables and/or graphs. The number and percentage of patients treated, and the primary reason for discontinuation will be displayed. Demographic variables (such as age) and baseline characteristics will be summarized by descriptive statistics. Compliance with pembrolizumab administration will be measured by patients: 1) receiving unscheduled study agent infusions/injections; 2) missing an infusion/injection. Numbers and percentages of patients and infusion/injection visits with any deviation in these measures will be reported.
|Study Start Date:||May 2015|
|Estimated Study Completion Date:||March 2019|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
I. To evaluate objective response rate (ORR) in patients with advanced uveal melanoma receiving pembrolizumab.
I. To evaluate progression-free survival (PFS) in patients with advanced uveal melanoma receiving pembrolizumab.
II. To evaluate safety, tolerability and adverse experience profile of pembrolizumab in uveal melanoma.
III. To evaluate overall survival (OS) in patients with advanced uveal melanoma receiving pembrolizumab.
I. To evaluate objective response rate (ORR; complete response + partial response) in patients with advanced uveal melanoma receiving pembrolizumab as stratified by programmed cell death-ligand 1 (PD-L1) expression and guanine nucleotide-binding protein (GNA)Q/GNA11 mutation status.
II. To evaluate ORR in patients previously treated with ipilimumab or with mitogen-activated protein kinase kinase (MEK) inhibitors.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02359851
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Douglas Johnson||Vanderbilt-Ingram Cancer Center|