Study of the Drug Ipilimumab for Metastatic Merkel Cell Carcinoma
- Ipilimumab is a drug used to treat melanoma that cannot be treated surgically. It targets a molecule found on T-cells in the human immune system. Blocking these molecules on the T-cells might allow the cells to help destroy melanoma cells more effectively. This drug has also been studied in other cancers such as prostate cancer and lung cancer, but not yet in Merkel cell carcinoma (MCC). Researchers think therapy like ipilimumab that enhances the immune system may be effective against MCC. They want to study how safe the drug is and its effect on the immune system and tumors.
- To determine the number of subjects with MCC who take the study drug that remain alive 12 months later.
- Adults 18 years and older who have metastatic MCC.
- Participants will be screened with a medical history and physical exam.
- Participants will receive the study drug 4 times, one dose every 21 days. After the 4 visits, participants will receive a maintenance dose of the drug every 12 weeks until the drug is no longer beneficial.
- They will receive the drug through a plastic tube usually inserted in a vein on the arm.
- It will take 90 minutes to give each dose.
- At all visits, participants will be screened with a medical history, physical exam, and blood tests. Any tumors on their skin will be measured and photographed.
- Every 12 weeks during the study and maintenance period, participants will have a CT scan. Throughout the study and maintenance period, they will have blood and skin tests.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Open-Label Trial of Ipilimumab for Metastatic Merkel Cell Carcinoma|
- Overall survival at 12 months with ipilimumab treatment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Determine the best overall response rate, median survival, disease-specific survival, and progression free survival. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Determine median survival, disease-specific survival, and progressionfree survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2013|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cancer of the skin with a mortality of approximately 33%. Approximately one-third of patients present with metastatic disease, for which there is no effective treatment. Merkel cell polyomavirus (MCV), a DNA virus that expresses T antigen oncoproteins, was found to be clonally integrated into the genome of the majority of MCC tumors. MCC tumor progression is believed to be associated with the development of immune evasion, and multiple lines of evidence (higher incidence in immunocompromised populations, reports of spontaneous regression, responses to immune modulators, and improved prognosis associated with CD8+ intratumoral lymphocytes) suggest that immunotherapy may improve outcomes in patients with advanced MCC. Ipilimumab is a recombinant, human monoclonal antibody that binds to cytotoxic Tlymphocyte- associated antigen 4 and has shown efficacy in metastatic melanoma.
-Determine overall survival at 12 months.
- Determine the best overall response rate, as assessed by modified RECIST immunerelated response criteria, at week 12.
- Determine median survival.
- Determine disease-specific survival (DSS) and progression-free survival (PFS).
- Evaluate the safety and tolerability of ipilimumab in patients with metastatic MCC.
- Assess biomarkers of immune activation and MCV-specific immune response.
- Patients (age greater than or equal to 18 years) with metastatic MCC (AJCC stage 3b or 4).
- Immunocompromised individuals and patients with autoimmune disease are excluded.
- Patients will enroll at the NIH Clinical Center, Bethesda, MD (primary site) or at a study sub-sites Memorial Sloan-Kettering Cancer Center, New York, NY; University of Michigan, Ann Arbor, MI; or University of Pennsylvania, Philadelphia, PA.
- Ipilimumab will be given at a dose of 10 mg/kg as a 90-minute intravenous infusion on day 1 of each 21-day cycle for 4 cycles. After 4 doses, patients may receive a maintenance dose every 12 weeks until disease progression or unacceptable toxicity, for up to an additional 4 doses.
- Imaging scans will be done at week 12, and every 12 weeks on study starting week 21.
- Patients will remain on-study for follow-up for 96 weeks after the last of the initial 4 doses.
- Response and progression will be evaluated using modified RECIST immune-related response criteria.
|Principal Investigator:||Isaac F Brownell, M.D.||National Cancer Institute (NCI)|