Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma That Has Not Responded to Previous Treatment

NCT ID: NCT00022438

Last Updated: 2013-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-06-30
• Study Completion Date: 2004-08-31

Brief Summary

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. Combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma.

PURPOSE: Randomized phase II trial to compare the effectiveness of vaccine therapy plus interleukin-2 to that of vaccine therapy alone in treating patients who have metastatic melanoma that has not responded to previous treatment.

Detailed Description

OBJECTIVES:

• Determine the clinical responses in patients with HLA-A0201-positive refractory metastatic melanoma treated with tyrosinase-related protein-2:180-188 peptide vaccine alone.
• Determine the clinical response rate of patients who have an immediate need to receive interleukin-2 (IL-2) in addition to this vaccine.
• Compare the immunologic response, in terms of changes in T-cell precursors before and after treatment, in patients treated with this vaccine with or without IL-2.
• Compare the toxicity profile of these regimens in these patients.

OUTLINE: This is a randomized, open-label study.

Patients who need immediate interleukin-2 (IL-2) receive tyrosinase-related protein-2 (TRP-2):180-188 peptide vaccine emulsified with Montanide ISA-51 on day 1 and high-dose IL-2 IV over 15 minutes once every 8 hours on days 2-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who do not need immediate IL-2 are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 subcutaneously (SC) on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 SC once weekly on weeks 1-4. Treatment repeats every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who have a complete response (CR) receive 1 additional course after achieving CR. Patients who have progressive disease while receiving vaccine alone may cross over to receive peptide vaccine with IL-2 for at least 2 courses.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A maximum of 83 patients (19-33 who need immediate interleukin-2 (IL-2); 15-25 per treatment arm who do not need immediate IL-2) will be accrued for this study within 1 year.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

recombinant tyrosinase-related protein-2

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma

• Refractory to standard therapy
• No resectable locoregional disease
• HLA-A0201 positive
• Measurable disease
• Previously resected brain metastases, brain metastases stable after prior radiosurgery, or brain metastases less than 1 cm and without edema allowed

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 90,000/mm^3
• No coagulation disorders

Hepatic:

• Bilirubin no greater than 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)
• AST/ALT less than 3 times normal
• Hepatitis B surface antigen negative

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No major medical illness of the cardiovascular system
• No cardiac ischemia*
• No myocardial infarction*
• No cardiac arrhythmias* NOTE: * For interleukin-2 (IL-2) administration

Pulmonary:

• No major medical illness of the respiratory system
• No obstructive or restrictive pulmonary disease (for IL-2 administration)

Immunologic:

• HIV negative
• No primary or secondary immunodeficiency
• No known immunodeficiency disease
• No autoimmune disease
• No active systemic infections

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior biologic therapy for melanoma
• No prior immunization to tyrosinase-related protein-2 antigen
• No other concurrent biologic therapy for melanoma

Chemotherapy:

• At least 3 weeks since prior chemotherapy for melanoma and recovered
• No concurrent chemotherapy for melanoma

Endocrine therapy:

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

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy for melanoma and recovered
• No concurrent radiotherapy for melanoma

Surgery:

• See Disease Characteristics

Other:

• No other concurrent therapy for melanoma

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Steven A. Rosenberg, MD, PhD

Role: STUDY_CHAIR

NCI - Surgery Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

NCI-01-C-0193

Identifier Type: -

Identifier Source: secondary_id

NCI-5369

Identifier Type: -

Identifier Source: secondary_id

CDR0000068818

Identifier Type: -

Identifier Source: org_study_id

NCT00017849

Identifier Type: -

Identifier Source: nct_alias