A Phase II Study of MK-3475 in Patients With Advanced Merkel Cell Carcinoma (MCC)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Recurrent Merkel Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 50
- Locations
- 13
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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 Description
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. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have biopsy-proven metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy
- •Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by computed tomography (CT) scan, or for skin lesions not measurable by CT scan, measurements may be performed with caliper or flexible ruler
- •Note: stage IV no evidence of disease (NED) is excluded by this criterion
- •Have a performance status of =\< 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Life expectancy of greater than 6 months
- •Leukocytes \>= 2,000/mcL (labs should be performed within 14 days of treatment initiation)
- •Absolute neutrophil count \>= 1,500/mcL (labs should be performed within 14 days of treatment initiation)
- •Platelets \>= 100,000/mcL (labs should be performed within 14 days of treatment initiation)
- •Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L (labs should be performed within 14 days of treatment initiation)
- •Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (labs should be performed within 14 days of treatment initiation)
Exclusion Criteria
- •Patient has had prior systemic therapy for MCC
- •Note: prior systemic cytotoxic chemotherapy will be allowed if it was administered in the adjuvant setting (no clinically detectable MCC at the time) and treatment concluded more than 6 months prior to beginning study treatment
- •Patient is currently participating in or has participated in a study of an investigational systemic agent to treat MCC; or is using an investigational device within 4 weeks of the first dose of treatment
- •NOTE: if patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Toxicity from surgery or associated interventions that has not recovered to =\< grade 1 is allowed if it meets the inclusion requirements for laboratory parameters
- •Patients with locoregional disease that have not received appropriate standard locoregional therapy with surgery and/or radiation therapy
- •Patient has had radiation therapy within 2 weeks of beginning study treatment
- •Toxicity from prior radiation therapy has NOT resolved to grade 1 or less
- •Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial treatment
- •Patient has had a prior monoclonal antibody for treatment of MCC
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Progression-free Survival (PFS) Using RECIST 1.1(Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 16 months)
- Duration of Response (DOR)(Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 3 years)
- Overall Survival (OS)(Time interval between the start of treatment to death due to any cause, assessed up to 60 months.)
- Incidence of Adverse Events (AEs) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0(Up to 90 days post-treatment)