A Phase II Trial of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (Reolysin®) in Patients With Metastatic Melanoma
18 Years
N/A
Both
Recurrent Melanoma, Stage IV Melanoma
Trial Information
A Phase II Trial of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (Reolysin®) in Patients With Metastatic Melanoma
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
Inclusion Criteria:
- Histologically or cytologically confirmed malignant melanoma
- All melanomas, regardless of origin, are allowed
- Metastatic disease
- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20mm by conventional techniques or
as ≥ 10 mm by spiral CT scan
- Must have ≥ 1 metastatic lesion that can be safely biopsied
- Must have received ≥ 1 prior treatment for metastatic disease
- Not a candidate for curative surgery for metastatic disease
- No known brain metastases
- ECOG performance status 0-2
- Life expectancy > 12 weeks
- Total WBC ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN
- Troponin-T normal
- LVEF ≥ 50% by ECHO or MUGA
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Agrees to provide blood and tissue samples for the mandatory translational research
component of the study
- Must be able to avoid direct contact with pregnant or nursing women, infants, and
immuno compromised individuals during study and for ≥ 3 weeks following the last dose
of study agent
- No concurrent uncontrolled illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris, cardiac arrhythmia, or myocardial infarction within
the past year
- Psychiatric illness/social situation that would preclude study compliance
- No known HIV positivity
- Patients with a clinical history suggestive of an immuno compromised status are
required to undergo HIV testing
- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
and recovered
- More than 2 weeks since prior radiotherapy, immunotherapy, or treatment with small
molecule cell cycle inhibitors
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical benefit rate
Outcome Description:
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.
Outcome Time Frame:
Every 4 weeks during treatment, every 6 months for 2 years after treatment and then annually assessed up to 5 years
Safety Issue:
No
Principal Investigator
Evanthia Galanis
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00233
NCT ID:
NCT00651157
Start Date:
April 2008
Completion Date:
Related Keywords:
- Recurrent Melanoma
- Stage IV Melanoma
- Melanoma
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
