Vaccine Therapy in Treating Patients With Metastatic Melanoma

Immunization of Patients With Metastatic Melanoma Using Recombinant Fowlpox and Vaccinia Viruses Encoding the Tyrosinase Antigen

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with and without interleukin-2 in treating patients who have metastatic melanoma that has not responded to previous treatment.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: aldesleukin; Biological: fowlpox virus vaccine vector; Biological: vaccinia-tyrosinase vaccine

Detailed Description

OBJECTIVES:

• Determine efficacy of recombinant fowlpox and vaccinia viruses encoding tyrosinase antigen, administered with or without low-dose interleukin-2 (IL-2), in terms of response, in patients with metastatic melanoma.
• Compare the response rate in patients to this vaccination administered with high-dose IL-2 to that in similar patients on previous trials treated with high-dose IL-2 alone.
• Determine the immunological response in patients treated with this regimen.

OUTLINE: This is a randomized study. Patients are randomized to one of three treatment arms.

• Arm I: Patients receive recombinant fowlpox vaccine IM on day 1 followed 4 weeks later by recombinant vaccinia vaccine IM. Treatment repeats for a minimum of 4 vaccinations.
• Arm II: Patients receive vaccinations as in arm I plus low-dose interleukin-2 (IL-2) subcutaneously daily on days 2-13 after each vaccination.
• Arm III: Patients receive vaccinations as in arm I plus high-dose IL-2 IV over 15 minutes every 8 hours on days 2-5 after each vaccination.

Patients with stable disease or a minor, mixed, or partial response after four immunizations (1 course) may receive a second course of the same regimen beginning 4-6 weeks after the first course. After the second course, patients with tumor regression may continue to receive treatment in the absence of unacceptable toxicity until best response is achieved.

Patients are followed at 4-6 weeks.

PROJECTED ACCRUAL: A total of 73 patients (13-20 for arm I, 13-20 for arm II, and 19-33 for arm III) will be accrued for this study within 2 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Surgery Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma that has failed standard treatment
• No ocular or mucosal melanoma as primary site
• Measurable disease
• No existing brain metastases

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0 or 1

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm3
• Platelet count at least 90,000/mm3
• No coagulation disorder

Hepatic:

• Bilirubin no greater than 1.6 mg/dL
• AST/ALT less than 3 times normal
• Hepatitis B surface antigen negative

Renal:

• Creatinine no greater than 1.6 mg/dL

Cardiovascular:

• No major cardiovascular illness

Pulmonary:

• No major respiratory illness

Immunologic:

• HIV negative
• No autoimmune disease
• No primary or secondary immunodeficiency
• No allergy to eggs
• No history of allergy or untoward reaction to prior smallpox vaccination

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be able to avoid close contact with children under 5 years, pregnant women, people with active or a past history of eczema or other eczematoid skin disorders, and immunosuppressed people for at least 2 weeks after each vaccinia virus vaccination
• No active systemic infections
• No active atopic dermatitis or active or past history of eczema
• No concurrent active extensive psoriasis, severe acneiform rash, impetigo, varicella zoster, burns, or other traumatic or pruritic skin conditions or open wounds
• Surgical scars must be healed
• Healed surgical stomas (e.g., colostomy) allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior recombinant vaccinia or fowlpox vaccines for melanoma
• At least 3 weeks since prior systemic biologic therapy for melanoma

Chemotherapy:

• At least 3 weeks since prior systemic chemotherapy for melanoma

Endocrine therapy:

• At least 3 weeks since prior systemic endocrine therapy for melanoma
• No concurrent steroid therapy

Radiotherapy:

• At least 3 weeks since prior systemic radiotherapy for melanoma

Surgery:

• Prior surgery allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Suzanne L. Topalian, MD, NCI - Surgery Branch

Study record dates

Study Major Dates

• Study Start: July 1, 1999
• Study Completion (Actual): May 1, 2003

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: May 27, 2003
• First Posted (Estimate): May 28, 2003

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: May 1, 2007

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV 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; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Immunologic Factors; Aldesleukin; Vaccines
• Other Study ID Numbers: CDR0000067075; NCI-99-C-0095; NCI-T99-0025