Vaccine Therapy in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from DNA may help the body build an effective immune response to kill tumor cells. Giving the vaccine in different ways may make a stronger immune response and kill more tumor cells. PURPOSE: This randomized clinical trial is studying two different ways of giving vaccine therapy to compare how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Evaluate the safety and feasibility of particle-mediated epidermal delivery (PMED) immunization comprising mouse gp100 plasmid DNA vaccine in patients with stage IIB, IIC, III, or IV melanoma. Compare the immunologic response induced with PMED vs intramuscular jet injection methods of vaccination in these patients. Secondary Observe patients with measurable tumor for evidence of any antitumor response generated after vaccination. Assess for disease relapse in patients treated with this vaccine. OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive mouse gp100 plasmid DNA vaccine by particle-mediated epidermal delivery on days 1, 3, 5, 8, 22, 24, 26, 29, 43, 45, 47, 50, 64, 66, 68, and 71. Arm II: Patients receive mouse gp100 plasmid DNA vaccine by intramuscular jet injection on days 1, 3, 5, 8, 22, 24, 26, 29, 43, 45, 47, 50, 64, 66, 68, and 71. After completion of study treatment, patients are followed periodically for 1 year.

Official Title
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Injection of AJCC Stage IIB, IIC, III and IV Melanoma Patients With Mouse gp100 DNA: A Pilot Study to Compare Intramuscular Jet Injection With Particle Mediated Delivery

Conditions
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Melanoma (Skin), Intraocular Melanoma

Intervention / Treatment
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* Biological: mouse gp100 plasmid DNA vaccine
* Device: The Dermal PowderMed® devices
* Other: intramuscularly (IM injection)


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma Stage IIB, IIC, III, or IV disease Patients free of disease after surgical resection must meet 1 of the following criteria: Refused high-dose interferon alfa Recurrence while on interferon alfa Patients with stage IIB, IIC, or III disease must have already undergone initial standard therapy (i.e., surgery) for the disease Choroidal (uveal) melanoma allowed provided 1 of the following criteria is met: Basal diameter > 16 mm Basal height > 8 mm Involvement of the ciliary body with tumor HLA-A*0201 positive Negative serum antidouble-stranded DNA antibody screen No known brain metastases PATIENT CHARACTERISTICS: Karnofsky performance status 80-100% Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 WBC ≥ 3,000/mm^3 Lactic dehydrogenase ≤ 2 times upper limit of normal (ULN) Creatinine ≤ 2.0 mg/dL Bilirubin ≤ 2.5 times ULN Albumin ≥ 3.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Weight ≥ 25 kg No preexisting choroidal eye disease No serious underlying medical conditions that could be exacerbated by study participation (i.e., active infections requiring antimicrobial drugs or active bleeding) No allergy to gold (i.e., gold jewelry) No evidence of any condition at the proposed site(s) of vaccine administration that might interfere with the interpretation of local skin reactions, including any of the following: Damaged skin Moles Scars Tattoos Marks No prior medical condition or use of medication (e.g., corticosteroids) that might make it difficult for the patient to complete the full course of treatment or to respond immunologically to vaccines No history or evidence (within the past 5 years) of a physician-diagnosed chronic or recurrent inflammatory skin disease at the proposed site of vaccine administration, including any of the following: Psoriasis Eczema Atopic dermatitis Hypersensitivity No history of keloid formation PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior chemotherapy, immunotherapy, or radiotherapy (6 weeks for nitrosoureas) and recovered No prior immunization with any class of vaccine containing gp100 peptide No other concurrent investigational agents No other concurrent systemic therapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mouse gp100 DNA via PMED<br>patients will be randomized to mouse gp100 DNA delivered via gold particles using the PowderMed delivery system (ND10, described above). Two actuations/day will be administered every two weeks for 4 months for a total of 16 actuations. Each actuation consists of 2 μg of plasmid DNA coated onto 1000 μg of gold. The total dose of plasmid DNA given will be 32 μg DNA on 16,000 μg gold. | Biological: mouse gp100 plasmid DNA vaccine<br> <br> Device: The Dermal PowderMed® devices<br> <br> |
| Experimental: mouse gp100 DNA injections intramuscularly<br>patients will be injected with 1000 μg of mouse gp100 plasmid DNA intramuscularly. Two injections/day will be administered every two weeks for 4 months (4000 ug of mouse gp100 plasmid/month) for 16 vaccinations. | Biological: mouse gp100 plasmid DNA vaccine<br> <br> Other: intramuscularly (IM injection)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Evulated for Toxicity and Safety | All toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v3.0. | 2 years | 
| Number of Participants With a T-cell Response | T-cell response: Peripheral blood lymphocytes will be tested for reactivity against gp100 using an IFN-y ELISPOT, intracellular cytokine staining or MHC tetramer assay. If T-cell reactivity is induced, additional samples may be drawn to determine the duration of this reactivity. Follow-up blood samples require only 20-30 ml. MHC tetramer assays and intracellular flow cytometry studies may also be performed. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Response | In patients with measurable disease, the RECIST criteria for anti-tumor effect will be used. Lesions will be defined as measurable if they can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm by spiral CT scan.Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, ciliary body and choroid melanoma, small size, recurrent intraocular melanoma, metastatic intraocular melanoma