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Viral Therapy in Treating Patients With Metastatic Melanoma

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
wild-type reovirus
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (viral therapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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 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.

Full Information

First Posted
April 1, 2008
Last Updated
March 21, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00651157
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (viral therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
wild-type reovirus
Other Intervention Name(s)
REOLYSIN
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tumor Response
Description
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.
Time Frame
Every 4 weeks after 4 courses of treatment, assessed up to 5 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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 Frame
Time from registration to death due to any cause, assessed up to 5 years
Title
Time to Disease Progression
Description
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 Frame
Time from registration to documentation of disease progression, assessed up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evanthia Galanis
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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Viral Therapy in Treating Patients With Metastatic Melanoma

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