Viral Therapy in Treating Patients With Metastatic Melanoma

Stage IV Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00651157
• Other study ID #: NCI-2009-00233
• Secondary ID: NCI-2009-00233MA
• Status: Completed
• Phase: Phase 2
• First received: April 1, 2008
• Last updated: March 21, 2014
• Start date: April 2008
• Est. completion date: October 2012

Study information

• Verified date: February 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• Eastern Cooperative Oncology Group performance status 0-2

• Life expectancy > 12 weeks

• Total White Blood Cell (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)

• Aspartate Aminotransferase (AST) = 2.5 times ULN

• Creatinine = 1.5 times ULN

• Troponin-T normal

• Left ventricular ejection fraction (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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Recurrent Melanoma
• Stage IV Melanoma

Intervention

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.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response	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.	Every 4 weeks after 4 courses of treatment, assessed up to 5 years	No
Secondary	Overall Survival	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 from registration to death due to any cause, assessed up to 5 years	No
Secondary	Time to Disease Progression	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.	Time from registration to documentation of disease progression, assessed up to 5 years	No