Vaccine Therapy in Treating Patients With Metastatic Melanoma
Study Details
Study Description
Brief Summary
Vaccines may make the body build an immune response to kill tumor cells. Injecting a vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. This phase II trial is studying how well vaccine therapy works in treating patients with metastatic melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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Determine the safety and tolerability of intratumoral fowlpox-TRICOM in patients with metastatic melanoma.
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Determine the local response rate in patients treated with this agent. III. Determine systemic clinical response in patients treated with this agent.
SECONDARY OBJECTIVES:
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Determine the increase in transgene expression of B7-1, leukocyte function-associated antigen-3 (LFA-3), and intercellular adhesion molecule-1 (ICAM-1) in patients treated with this agent.
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Determine the effects of this agent on CD8-positive antitumor T-cell frequency as measured by tetramer and ELISpot in patients who are HLA-A2 positive.
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Correlate transgene expression of B7-1, LFA-3, and ICAM-1 by tumor cells with changes in function or number of melanoma antigen-specific CD8-positive T lymphocytes in patients treated with this agent.
OUTLINE: This is a multicenter study.
Patients receive fowlpox-TRICOM intratumorally on day 1 of weeks 1, 4, and 7 (maximum of 3 injections for a single lesion) (course 1). After 3 injections (course 1), patients with stable or responding disease receive additional injections into new lesions following the same schedule as above. Treatment repeats every 9 weeks for a maximum total of 9 injections (3 injections total into a maximum of 3 different tumors) (total of 3 courses) in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then approximately every 6 months for 5-15 years.
PROJECTED ACCRUAL: A total of 14-28 patients will be accrued for this study within 14-28 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (recombinant fowlpox-TRICOM vaccine) Patients receive fowlpox-TRICOM intratumorally on day 1 of weeks 1, 4, and 7 (maximum of 3 injections for a single lesion) (course 1). After 3 injections (course 1), patients with stable or responding disease receive additional injections into new lesions following the same schedule as above. Treatment repeats every 9 weeks for a maximum total of 9 injections (3 injections total into a maximum of 3 different tumors) (total of 3 courses) in the absence of disease progression or unacceptable toxicity |
Biological: recombinant fowlpox-TRICOM vaccine
Given intratumorally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Local response defined as complete response (CR), a partial response (PR) stable disease (SD), or progressive disease (PD) in the injected lesion according to RECIST criteria [Up to 15 years]
- Overall clinical response (CR or PR) as measured by RECIST criteria [Up to 15 years]
Secondary Outcome Measures
- Change in mRNA expression of B7-1, LFA-3, and/or ICAM-1in the tumor microenvironment [Baseline and week 10]
Changes in laboratory correlates pre- versus post- treatment will be analyzed using a paired t-test. The association between changes in these measurements and tumor response will be assessed by comparing the changes in responders and non-responders using a Wilcoxon rank-sum test.
- Changes in tumor associated T cells [Baseline and week 10]
Changes in laboratory correlates pre- versus post- treatment will be analyzed using a paired t-test. The association between changes in these measurements and tumor response will be assessed by comparing the changes in responders and non-responders using a Wilcoxon rank-sum test.
- Time to tumor progression [Up to 15 years]
Time to tumor progression will be analyzed by the Kaplan-Meier method.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed melanoma
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Stage IV disease
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Measurable disease
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At least 1 cutaneous or lymph node mass ≥ 1 cm AND amenable to biopsy and percutaneous injection AND can be accurately measured with standard calipers
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Must be tested for expression of HLA-A2 prior to study
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Must have 1 of the following criteria:
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Circulating melanoma-specific CD8-positive T cells against ≥ 1 defined antigen (Melan-A, gp100 antigen, tyrosinase, MAGE-A10, Trp-2, or NA17) as measured by tetramer or ELISpot directly ex-vivo or after a 10 day in vitro expansion
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Detectable intratumoral T cells measured in the index lesion that is to be injected with rF-TRICOMTM by immunohistochemistry (IHC) for CD4, CD8 or another T cell marker, or by real time RT-PCR for CD8a, CD4, or other T cell transcripts
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No untreated or edematous brain metastases or leptomeningeal disease
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Treated CNS disease allowed provided patient remains stable off corticosteroid therapy
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Performance status - Karnofsky 70-100%
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More than 12 weeks
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WBC ≥ 3,000/mm^3
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Platelet count ≥ 100,000/mm^3
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No uncontrolled bleeding disorder that would increase the risk of bleeding from the injected lesion
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No active thrombotic thrombocytopenic purpura within the past 2 years
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PT/PTT ≤ 1.25 times upper limit of normal (ULN)
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AST and ALT ≤ 1.5 times ULN
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Bilirubin ≤ 1.5 times ULN
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No chronic hepatitis B or C
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Creatinine ≤ 2.0 mg/dL
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Creatinine clearance ≥ 60 mL/min
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No symptomatic congestive heart failure
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No unstable angina pectoris
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No cardiac arrhythmia
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HIV negative
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No prior significant allergic reaction or hypersensitivity to eggs or egg products
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No disease that limits the function of the spleen (e.g., sickle cell disease)
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No uncontrolled active or chronic infection
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No active autoimmune disorders or disease
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No immunosuppression, defined as concurrent or possible requirement for systemic corticosteroids
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception during and for at least 4 weeks after study participation
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Able to avoid direct contact of the immunization site with the following individuals:
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Children < 3 years of age
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Immunocompromised individuals (including those on systemic corticosteroids)
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Pregnant women
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Individuals with extensive skin disease
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No active seizure disorder
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No skin disease and/or open unhealing wounds
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No psychiatric illness or social situation that would preclude study compliance
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No other significant medical illness that would significantly increase the risk associated with immunotherapy
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No other active malignancy requiring concurrent therapy except squamous cell or basal cell skin cancer or undetectable hormone-responsive prostate cancer (as measured by normal prostate-specific antigen)
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No other concurrent uncontrolled illness that would preclude study participation
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No prior fowlpox virus-based therapy
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No prior B7-1, intercellular adhesion molecule-1 (ICAM-1), or leukocyte function-associated antigen-3 (LFA-3)
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More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
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See Disease Characteristics
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Concurrent adjuvant hormonal therapy for early-stage or high-risk breast cancer allowed
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No concurrent corticosteroids
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More than 2 weeks since prior radiotherapy and recovered
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More than 2 weeks since prior surgery and recovered
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No prior splenectomy
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No concurrent therapeutic anticoagulation therapy that would increase the risk of bleeding from injected lesion
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No other concurrent immunosuppressive drugs
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No other concurrent investigational agents
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No other concurrent anticancer therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Chicago | Chicago | Illinois | United States | 60637 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Thomas Gajewski, University of Chicago
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02615
- NCI-2012-02615
- CDR0000374979
- UCCRC-12759A
- NCI-6038
- 12759A
- 6038
- P30CA014599