Up to 24 patients with stage III or stage IV melanoma will be enrolled. Patients who are currently disease-free but at high risk for relapse are also eligible. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are eligible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies.

Condition	Treatment or Intervention	Phase
Malignant Melanoma	Vaccine: gp75 DNA vaccine	Phase I

This study is designed to evaluate the safety and feasibility of intramuscular vaccination with gp75 DNA in patients with stage III or IV melanoma. Secondary objectives are to observe the patient for any evidence of anti-tumor response and to establish the optimal biologically effective dose. Up to 24 evaluable patients with stage III or IV metastatic melanoma or with stage III melanoma, currently disease-free, but at high risk for recurrence will be enrolled. Patients will be be enrolled into an assigned dose group and will receive five vaccinations of gp75. In order for dose escalation to proceed, only one patient in the current dose group may have demonstrated a dose limiting toxicity (DLT). If a second patient experiences such toxicity then both patients will move down to the previous dose level, and the previous dose level will be considered to be the MTD. If no DLTs are encountered, patients will continue on study at the assigned dose level. Any patient experiencing a DLT will not receive further vaccination until the toxicity has resolved. Patients exhibiting both serological and stable/clinical response after receiving the fifth vaccination will be eligible to receive booster vaccinations. An additional patient will be accrued to the dose level for every patient that progresses prior to the fifth vaccination.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Age 18 years or older with Karnofsky performance status of 80 or greater, with a diagnosis of AJCC stage III or IV malignant melanoma. Patients free of disease after surgical resection of stage III or IV disease, but at high risk (defined as a primary tumor > 4 mm, satellite or in-transit lesions, 1 or more positive lymph nodes or distant metastases) for recurrence are also eligible. No more than five sites of metastatic disease permitted.
• Patient has given signed informed consent
• Patient has had surgery for their melanoma at least 6 months prior to study entry, or has had prior interferon therapy, or developed unacceptable toxicities to interferon therapy, or has a pre-existing condition(s) that precludes the patient from receiving interferon treatment
• Patient has completed any prior irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) at least 30 days prior to study entry
• Adequate hematologic function: platelet count ³ 100,000/mm3; WBC level ³ 3,000/mm3
• Normal serum LDH and a serum creatinine level < 2.0 mg/dL
• Agrees to use effective contraception if procreative potential exists

Exclusion Criteria:

• Patient has stage III disease otherwise eligible to receive standard of care melanoma therapy.
• Patient has a medical condition or uses medication (eg, corticosteroids) that might make it difficult for the patient to complete the full course of treatments or to respond immunologically to them, in the opinion of the investigator.
• The patient has received irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) within 30 days prior to study entry
• Patient is pregnant (confirmed by serum beta human chorionic gonadotropin [bHCG], if applicable) or is breast feeding.
• Patient has received an investigational agent within 30 days of study entry
• Patient has received prior cancer vaccine therapy
• Patient has evidence of central nervous system (CNS) metastasis
• The patient has evidence of an ocular abnormality, as detected by a slit-lamp ophthalmologic examination, within 4 weeks prior to study entry

New York
      MSKCC Memorial Hospital, New York,  New York,  10021,  United States; Recruiting

Study ID Numbers:  CP09-0001
Record last reviewed:  November 2004
Record first received:  April 30, 2002
ClinicalTrials.gov Identifier:  NCT00034554
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-10