A Phase II Trial of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (Reolysin®) in Patients With Metastatic Melanoma
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical benefit rate
Clinical benefit rate defined as the number of patients who remain on study treatment and whose disease either meets the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for complete response [CR] or partial response [PR] on two consecutive evaluations at least 4 weeks apart or meets the RECIST criteria for STABLE disease at least 8 weeks post-registration divided by the number of patients who met the eligibility criteria, signed a consent form and begun treatment.
Every 4 weeks during treatment, every 6 months for 2 years after treatment and then annually assessed up to 5 years
United States: Food and Drug Administration
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