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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: mouse gp100 plasmid DNA vaccine; Biological: human gp100 plasmid DNA vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: human gp100 DNA vaccine; 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: mouse gp100 plasmid DNA vaccine; Biological: human gp100 plasmid DNA vaccine
Experimental: mouse gp100 DNA vaccine; 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: mouse gp100 plasmid DNA vaccine; Biological: human gp100 plasmid DNA vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety and feasibility	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jedd D. Wolchok, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: March 3, 2005
• First Submitted That Met QC Criteria: March 3, 2005
• First Posted (Estimate): March 4, 2005

Study Record Updates

• Last Update Posted (Estimate): March 12, 2013
• Last Update Submitted That Met QC Criteria: March 11, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage III melanoma; stage II melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 03-007; P30CA008748 (U.S. NIH Grant/Contract); MSKCC-IRB-03007