Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer
|Recurrent Merkel Cell Carcinoma Stage III Merkel Cell Carcinoma AJCC v7 Stage IIIA Merkel Cell Carcinoma AJCC v7 Stage IIIB Merkel Cell Carcinoma AJCC v7 Stage IV Merkel Cell Carcinoma AJCC v7||Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Study of MK-3475 in Patients With Advanced Merkel Cell Carcinoma (MCC)|
- Objective response rate (ORR) defined as the proportion of patients who have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3 years ]ORR will be estimated as the number of responders as a percent of the number of eligible participants who received at least one dose of treatment. If a substantial amount of data is missing, analyses will be performed using parametric generalized linear models fit by maximum likelihood. A generalized linear model for the ORR will use a binomial error distribution. The model will include as covariates all available baseline predictors of the missing outcomes. Responses to continued pembrolizumab will be chronicled and reported.
- Duration of response (DOR) [ Time Frame: Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 3 years ]Survival curves for DOR will be estimated using the Kaplan-Meier method.
- Incidence of adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 90 days post-treatment ]Safety will be assessed by quantifying the toxicities and grades experienced by subjects including serious AEs (SAEs) and events of clinical interest. Safety and tolerability will be assessed by clinical review of all relevant parameters including AEs, laboratory tests, vital signs, and electrocardiogram measurements. Adverse experiences will be summarized as counts and frequencies by toxicity grade. Summary statistics (median and range) for time to onset of first drug-related toxicity will be provided.
- Overall survival (OS) [ Time Frame: Time interval between the start of treatment to death due to any cause, assessed up to 3 years ]Survival curves for OS will be estimated using the Kaplan-Meier method.
- Progression-free survival (PFS) using RECIST 1.1 [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 16 months ]Survival curves for PFS will be estimated using the Kaplan-Meier method.
- Immune correlates of the clinical activity of pembrolizumab [ Time Frame: Baseline ]This will include immunohistochemical and gene expression analysis focusing on delineating the immune components and immunologic milieu within the tumor before therapy.
- Merkel polyomavirus (MCPyV)-specific immune response, assessed with enzyme-linked immunosorbent spot and serology assays [ Time Frame: After 2 years of treatment ]Responses will be assessed at baseline, after initiating therapy, and correlated with clinical responses over time. Among patients with corresponding MHC-peptide tetramers, pre- and post-treatment samples of circulating MCPyV-specific CD8 T cells will be isolated and subjected to deep immunophenotyping by messenger ribonucleic acid (mRNA) expression analysis.
|Actual Study Start Date:||November 25, 2014|
|Estimated Primary Completion Date:||January 20, 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 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity.
* NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years.
Other: Laboratory Biomarker Analysis
Ancillary studiesBiological: Pembrolizumab
I. To determine the clinical efficacy of MK-3475 (pembrolizumab) as the first systemic intervention for patients with advanced Merkel cell carcinoma (MCC).
I. To determine the clinical activity of MK-3475 as the first systemic intervention for patients with advanced MCC.
I. To determine the immune correlates of the clinical activity of MK-3475.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity.
* NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol principal investigator (P.I.) and Cancer Immunotherapy Trials Network (CITN) P.I. approval, patients may receive treatment beyond 2 years.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 1 year, every 6 months for 2 years, annually until the patient has completed 3 years of follow up for disease assessment, and then every 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02267603
|United States, California|
|Stanford Cancer Institute Palo Alto|
|Palo Alto, California, United States, 94304|
|UCSF Medical Center-Mount Zion|
|San Francisco, California, United States, 94115|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Louisiana|
|Louisiana State University Health Science Center|
|New Orleans, Louisiana, United States, 70112|
|University Medical Center New Orleans|
|New Orleans, Louisiana, United States, 70112|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, New York|
|Mount Sinai Hospital|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Paul Nghiem||Cancer Immunotherapy Trials Network|