Clinical Trial: Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Study of MK-3475 in Patients With Advanced Merkel Cell Carcinoma (MCC)

Brief Summary: This phase II trial studies how well pembrolizumab works in treating patients with Merkel cell cancer that cannot be removed by surgery or controlled with treatment, or has spread to other parts of the body. Pembrolizumab may stimulate the immune system to identify and destroy cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the clinical efficacy of MK-3475 (pembrolizumab) as the first systemic intervention for patients with advanced Merkel cell carcinoma (MCC).

SECONDARY OBJECTIVES:

I. To determine the clinical activity of MK-3475 as the first systemic intervention for patients with advanced MCC.

TERTIARY OBJECTIVES:

I. To determine the immune correlates of the clinical activity of MK-3475.

OUTLINE:

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.

After completion of study treatment, patients are followed up at 30 days and then every 9-12 weeks for 1 year.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response rate (ORR) defined as the proportion of patients who have achieved complete response (CR) or partial response (PR) according to RECIST version 1.1 [ Time Frame: Up to 1 year ]

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.


Original Primary Outcome: Objective response rate (ORR) defined as the proportion of patients who have achieved complete response (CR) or partial response (PR) according to RECIST version 1.1 [ Time Frame: Up to 4 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.


Current Secondary Outcome:

  • Duration of response (DOR) [ Time Frame: Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 1 year ]
    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 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 1 year ]
    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.


Original Secondary Outcome:

  • 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.
  • Duration of response (DOR) [ Time Frame: Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 4 years ]
    Survival curves for DOR will be estimated using the Kaplan-Meier method.
  • Overall survival (OS) [ Time Frame: Time interval between the start of treatment to death due to any cause, assessed up to 1 year ]
    Survival curves for OS 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 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.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 14, 2014
Date Started: November 2014
Date Completion:
Last Updated: May 12, 2017
Last Verified: May 2017