Vaccine Therapy in Treating Patients With Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of intranodal Synchrovax SEM plasmid DNA vaccine in patients with stage IV melanoma. Determine the safety and tolerability of this drug in these patients. Determine the immunological response, as measured by changes in frequency of T cells specific against vaccine-encoded epitopes before and after treatment, in patients treated with this drug. Determine the clinical response, as measured by lactic dehydrogenase levels and radiologic assessment of lesions, in patients treated with this drug. OUTLINE: This is a multicenter, dose-escalation study. Patients receive Synchrovax SEM plasmid DNA vaccine by continuous intranodal infusion on days 1-4. Treatment repeats every 14 days for up to 4 courses in the absence of unacceptable toxicity. Patients with evidence of stable or responding disease are eligible for 4 additional courses of treatment. Cohorts of 6 patients receive escalating doses of Synchrovax SEM plasmid DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 10 days after the last dose of study drug. PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study.

Official Title
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A Phase I/II Pilot Study Of Intranodal Delivery Of A Plasmid DNA (Synchrovax SEM Vaccine) In Stage IV Melanoma Patients

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: MKC1106-MT
* Biological: MKC1106-MT
* Biological: MKC1106-MT


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV melanoma Must have tumor tissue available for determining antigen expression At least 10% of tumor cells must stain positive for Melan-A/Mart-1 by immunohistochemistry HLA-A2 positive No brain metastases unless completely resected or without evidence of disease after treatment PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: More than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 WBC at least 3,000/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL Hepatic: SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Bilirubin no greater than 1.5 times ULN Hepatitis B surface antigen negative Hepatitis C antibody negative Renal: Creatinine no greater than 1.5 times ULN Urea no greater than 2.6 times ULN Other: Not pregnant, nursing, or planning to become pregnant within 6 months of treatment completion Negative pregnancy test Fertile patients must use effective contraception HIV negative No medical, sociological, or psychological impediments that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy At least 4 weeks since prior immunomodulatory drugs No other concurrent immunotherapy No concurrent immunomodulatory drugs Chemotherapy: At least 4 weeks since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 4 weeks since prior systemic corticosteroids No concurrent systemic corticosteroids Radiotherapy: At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 4 weeks since prior investigational drugs No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>The first cohort of 6 patients received 500 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort. | Biological: MKC1106-MT<br>* Cancer Vaccine, Immunotherapy, 500 ug<br>|
| Experimental: Cohort 2<br>The second cohort of 6 patients received 1000 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (<33%) patients of a 6 patient cohort. | Biological: MKC1106-MT<br>* Cancer Vaccine, Immunotherapy, 1000 ug<br>|
| Experimental: Cohort 3<br>The third cohort of 6 patients received 1500 ug of Synchrovax SEM plasmid DNA vaccine. The maximum tolerated dose (MTD) was to be determined by the observation of DLT at each dose group. | Biological: MKC1106-MT<br>* Cancer Vaccine, Immunotherapy, 1500 ug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of the study was to evaluate the safety and tolerability of Synchrovax® pSEM Vaccine measured by the adverse event and severe adverse event profile. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objective of the study was to determine the immunological response of patients as measured by tetramer assay and to assess clinical response by LDH levels and radiological assessment of lesions. |  |  | 

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