Expired Study
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Rochester, Minnesota 55905


Purpose:

This phase II trial is studying the side effects and how well viral therapy works in treating patients with metastatic melanoma. Viral therapy may be able to kill tumor cells without damaging normal cells


Study summary:

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.


Criteria:

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


Study is Available At:


Original ID:

NCI-2009-00233


NCT ID:

NCT00651157


Secondary ID:

MC0672


Study Acronym:


Brief Title:

Viral Therapy in Treating Patients With Metastatic Melanoma


Official Title:

A Phase II Trial of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (Reolysin®) in Patients With Metastatic Melanoma


Overall Status:

Active, not recruiting


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, I


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

47


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Evanthia Galanis
Principal Investigator
Mayo Clinic

Study Dates

Start Date:April 2008
Primary Completion Date:December 2011
Primary Completion Type:Actual
Verification Date:August 2012
Last Changed Date:September 12, 2012
First Received Date:April 1, 2008

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Fludeoxyglucose (FDG) uptake
Time Frame:At baseline and at 4 weeks after treatment initiation
Safety Issues:False
Description:A times series plot of FDG uptake will be constructed. This plot will be visually assessed for trends. A 95% confidence interval for the proportion of patients who have at least a 50% reduction from pre-treatment FDG uptake levels at 4 weeks post treatmen
Outcome Type:Secondary Outcome
Measure:p38 expression in pretreatment tumor specimens
Time Frame:At baseline
Safety Issues:False
Description:Point and interval estimates of the true proportion of patients with p38 positive disease who derive clinical benefit as well as point and interval estimates of the true proportion of patients with p38 negative disease who derive clinical benefit will be
Outcome Type:Secondary Outcome
Measure:Viral replication in metastatic melanoma deposits
Time Frame:At 1 week (7 days) after treatment initiation
Safety Issues:False
Description:A plot of viral replication 1 week post treatment versus clinical benefit (yes/no) will be constructed to visually assess whether viral replication differs between those who derive clinical benefit and those who do not derive clinical benefit. A plot of v
Outcome Type:Secondary Outcome
Measure:Immunologic parameters
Time Frame:At baseline, every other month for 1 year, and at 6 and 12 months after completion of treatment
Safety Issues:False
Description:For each of the immunologic parameters, a times series plot will be constructed. A grid reflecting the percent change from pretreatment levels will be constructed. This grid can be inspected to see if the changes seen in a given immunologic parameter diff
Outcome Type:Secondary Outcome
Measure:Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time Frame:Weekly during course , prior to subsequent treatment courses, and up to 5 years after completion of
Safety Issues:True
Description:A plot of viral replication 1 week post treatment versus development of a severe toxicity after the first cycle of treatment (yes/no) will be constructed to visually assess whether viral replication differs with respect to development of severe toxicity.
Outcome Type:Secondary Outcome
Measure:Time to disease progression
Time Frame:Time from registration to documentation of disease progression, assessed up to 5 years
Safety Issues:False
Description:Sites of progression will be noted. Time to event distributions will be estimated using the Kaplan-Meier method.
Outcome Type:Secondary Outcome
Measure:Survival time
Time Frame:Time from registration to death due to any cause, assessed up to 5 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Tumor response rate
Time Frame:Every 4 weeks after 4 courses of treatment, assessed up to 5 years
Safety Issues:False
Description:A tumor response is defined to be a CR or PR as defined by the RECISTcriteria noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate will be estimated by the number of patients whose disease meets the RE
Outcome Type:Primary Outcome
Measure:Clinical benefit rate
Time Frame:Every 4 weeks during treatment, every 6 months for 2 years after treatment and then annually assesse
Safety Issues:False
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

Study Interventions

Intervention Type:Biological
Name:wild-type reovirus
Description:Given IV
Arm Name:Treatment (vaccine therapy)
Other Name:REOLYSIN
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Treatment (vaccine therapy)

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (vaccine therapy)
Description: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.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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