Viral Therapy in Treating Patients With Metastatic Melanoma
Stage IV Melanoma
Biological: wild-type reovirus
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (Reolysin®) in Patients With Metastatic Melanoma|
- Tumor Response [ Time Frame: Every 4 weeks after 4 courses of treatment, assessed up to 5 years ] [ Designated as safety issue: No ]
A tumor response is defined to be a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the largest dimension (LD) of target lesions taking as reference the baseline sum LD.
- Overall Survival [ Time Frame: Time from registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
- Time to Disease Progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]Time to disease progression is defined as the time from registration to documentation of disease progression. If a patient dies without documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death.
|Study Start Date:||April 2008|
|Study Completion Date:||October 2012|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (viral therapy)
Patients receive wild-type reovirus (Reolysin®) IV administered at a dose of 3 x 10^10 TCID50/day in 250 mL 0.9% sodium chloride infused intravenously over 60 minutes daily on days 1-5 of each 28-day cycle. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Biological: wild-type reovirus
Given IV: Administered at a dose of 3 x 10^10 TCID50/day in 250 mL 0.9% sodium chloride infused intravenously over 60 minutes daily on days 1-5 of each 28-day cycle.
Other Name: REOLYSIN
I. Assess the antitumor effect of wild-type reovirus (Reolysin®), in terms of tumor response rate and clinical benefit rate (i.e., partial response and complete response), in patients with metastatic melanoma.
II. Assess the toxicity profile of Reolysin® in these patients.
I. Assess the progression-free survival and overall survival of these patients. II. Assess viral replication in metastatic melanoma deposits after intravenous administration of Reolysin®.
III. Assess the impact of pre-existing anti-reoviral immunity (as represented by p38 expression in pretreatment tumor specimens) on the efficacy and toxicity of Reolysin®.
IV. To measure the effect of Reolysin® on the immune system, in terms of dendritic cell activation, T-cell activation, presence of Treg cells in tumor specimens, and the frequency of T cells, B cells, NK cells, and peptide specific cytotoxic T lymphocytes reactive against melanoma differentiation antigen peptides (gp100, MART-1, and tyrosinase).
V. To assess the induction of melanoma specific immune response, in terms of the presence of melanoma differentiation antigens (gp100, MART-1, and tyrosinase) in tumor specimens.
OUTLINE: This is a multicenter study.
Patients receive wild-type reovirus (Reolysin®) IV over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo tumor tissue samples collection at baseline and at 1 week after initiation of treatment for correlative laboratory studies. Tissue samples are analyzed for p38/MAPK activation status by IHC; reoviral replication in metastatic deposits by electron microscopy; and immunologic parameters by IHC. Blood samples are collected at baseline and periodically during the study. Blood samples are analyzed for immunologic parameters by tetramer and ELISPOT technology and for neutralizing antibodies against reovirus.
After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00651157
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Evanthia Galanis||Mayo Clinic|