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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vaccines made from DNA may make the body build an effective immune response to kill tumor cells. PURPOSE: This randomized phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage IIB, stage IIC, stage III, or stage IV melanoma.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the safety and feasibility of vaccination with human and mouse gp100 DNA in patients with stage IIB, IIC, III, or IV melanoma. Determine the maximum tolerated dose of this regimen in these patients. Compare the antibody and T-cell response in patients treated with two different vaccination schedules. Secondary Assess antitumor response in patients treated with this regimen. OUTLINE: This is a randomized, crossover, dose-escalation study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive human gp100 DNA vaccine intramuscularly (IM) once in weeks 1, 4, and 7. Patients then receive mouse gp100 DNA vaccine IM once in weeks 10, 13, and 16. Arm II: Patients receive mouse gp100 DNA vaccine IM once in weeks 1, 4, and 7. Patients then receive human gp100 DNA vaccine IM once in weeks 10, 13, and 16. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 6-9 patients (at least 3 per treatment arm) receive escalating doses of human and mouse gp100 DNA vaccines until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 9 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed at 3 weeks and then annually for 15 years. PROJECTED ACCRUAL: Approximately 18-27 patients will be accrued for this study within 6-9 months.

Official Title
-----------------
Injection of AJCC Stage IIB, IIC, III, and IV Melanoma Patients With Human and Mouse gp100 DNA: A Phase I Trial to Assess Safety and Immune Response

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: human gp100 plasmid DNA vaccine
* Biological: mouse gp100 plasmid DNA vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma Stage IIB, IIC, III, or IV disease Patients with stage III or IV disease who are free of disease after surgical resection* are eligible Patients free of disease after surgical resection* must have refused high-dose interferon alfa OR experienced recurrent disease during prior treatment with interferon alfa NOTE: *Patients who underwent surgical resection must have had the surgery within the past year HLA-A0201 positive No detectable brain metastases PATIENT CHARACTERISTICS: Age Any age Performance status Karnofsky 80-100% Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL No active bleeding Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) Albumin ≥ 3.5 g/dL AST and ALT ≤ 2.5 times ULN Lactate dehydrogenase ≤ 2 times ULN No clinical history of hepatitis B or C Renal Creatinine ≤ 2.0 mg/dL Immunologic No clinical history of HIV No clinical history of HTLV-1 No active infection requiring antibiotics within the past 72 hours No history of collagen vascular, rheumatologic, or other autoimmune disorder No grade 1 fever within the past 72 hours Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Weight ≥ 25 kg No serious underlying medical condition that would preclude study participation No preexisting uveal or choroidal eye disease PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics More than 4 weeks since prior immunotherapy No prior immunization with any class of vaccine containing gp100, including whole cell, shed antigen, or cell lysate vaccines Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) Endocrine therapy No concurrent corticosteroids that would preclude study participation Radiotherapy More than 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics Other Recovered from all prior therapy No other concurrent medication that would preclude study participation No other concurrent investigational agents No other concurrent systemic therapy
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: human gp100 DNA vaccine<br>Patients receive human gp100 DNA vaccine intramuscularly (IM) once in weeks 1, 4, and 7. Patients then receive mouse gp100 DNA vaccine IM once in weeks 10, 13, and 16. | Biological: human gp100 plasmid DNA vaccine<br> <br> Biological: mouse gp100 plasmid DNA vaccine<br> <br> |
| Experimental: mouse gp100 DNA vaccine<br>Patients receive mouse gp100 DNA vaccine IM once in weeks 1, 4, and 7. Patients then receive human gp100 DNA vaccine IM once in weeks 10, 13, and 16 | Biological: human gp100 plasmid DNA vaccine<br> <br> Biological: mouse gp100 plasmid DNA vaccine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and feasibility |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose |  | 2 years | 
| antibody and T-cell response |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma