Vaccine Therapy in Treating Patients With Melanoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00020358

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Vaccine therapy may be an effective treatment for melanoma.

PURPOSE: Randomized phase II trial to study the effectiveness of three vaccine therapy regimens in treating patients who have melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: aldesleukin Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: tyrosinase peptide	Phase 2

Detailed Description

OBJECTIVES:

Compare the immunologic activity of three different schedules of peptide immunization with gp100:209-217 (210M) or gp100:17-25 antigen and tyrosinase:368-376 (370D), tyrosinase:240-251 (244S), tyrosinase:206-214 (closed to accrual 11/05/01), or tyrosinase-related protein-1 (ORF3):1-9 peptide (closed to accrual 11/05/01) emulsified in Montanide ISA-51 in patients with melanoma at high risk for recurrence.
Compare the response rate to treatment with interleukin-2 (IL-2) after being immunized with this regimen with the usual response rate to IL-2 in this patient population.
Determine whether an exploratory cohort of HLA-A2-positive patients demonstrate immunologic activity to immunization with 2 peptides emulsified together.

OUTLINE: This is a randomized study. Patients are stratified according to HLA type (A0201 vs A1 vs A3 vs A24 vs A31). (HLA-A24 and HLA-A31 closed to accrual 11/05/01). Patients are randomized to 1 of 3 treatment arms and are given an assigned vaccine, which is emulsified in Montanide ISA-51.

HLA typing:
HLA-A2: gp100:209-217 (210M) and tyrosinase:368-376 (370D)
HLA-A1: tyrosinase:240-251 (244S)
HLA-A3: gp100:17-25
HLA-A24: tyrosinase:206-214 (closed to accrual 11/05/01)
HLA-A31: tyrosinase-related protein-1 (ORF3):1-9 (closed to accrual 11/05/01)
Arm I: Patients receive assigned vaccine subcutaneously (SC) weekly for 10 weeks followed by 3 weeks of no treatment.
Arm II: Patients receive assigned vaccine SC on days 1, 22, 43, and 64.
Arm III: Patients receive assigned vaccine SC on days 1-4, 22-25, 43-46, and 64-67.

Treatment in all arms repeats every 13 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

After the completion of the randomized arms of HLA-A2 patients, additional HLA-A2 patients receive immunization with gp100:209-217 (210M) and tyrosinase:368-376 (370D) emulsified in Montanide ISA-51 SC once every 3 weeks for 4 courses.

Patients with progressive disease may receive interleukin-2 IV over 15 minutes every 8 hours for up to 4 days. Treatment repeats every 10-14 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or mixed or partial response to treatment may receive additional courses every 2 months.

Patients are followed at 6 months.

PROJECTED ACCRUAL: A total of 324 patients (19-33 per arm for the HLA-A0201 stratum, 13-16 per arm for the other 4 strata, and 33 per the additional HLA-A2 cohort) will be accrued for this study within 2 years. (HLA-A24 and HLA-A31 closed to accrual 11/05/01).

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Randomized Comparison of Three Schedules of Peptide Immunization in Patients With Stage II or III, or Completely Resected Metastatic Melanoma

Study Start Date :

Sep 1, 2000

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of melanoma, including one of the following characteristics:
Lesions at least 1.5 mm in thickness
At least 1 positive lymph node
Ulcerated lesion
Local recurrence
Metastatic lesions completely resected within the past 6 months
Clinically disease free within the past 6 weeks
HLA-A1, A3, A24, A31, or 0201 positive (HLA-A24 and HLA-A31 closed to accrual 11/05/01)
No ocular or mucosal melanoma

PATIENT CHARACTERISTICS:

Age:

16 and over

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Platelet count at least 90,000/mm^3

Hepatic:

Bilirubin no greater than 1.6 mg/dL (3.0 mg/dL in Gilbert's syndrome)
AST and ALT less than 3 times normal
Hepatitis B surface antigen negative

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

For interleukin-2 (IL-2) therapy:
No cardiac ischemia, myocardial infarction, or cardiac arrhythmias
Stress cardiac test required if abnormal EKG, symptoms of cardiac ischemia or arrhythmia, or older than 50 years

Pulmonary:

For IL-2 therapy:
No obstructive or restrictive pulmonary disease
FEV_1 greater than 60% predicted if prolonged history of cigarette smoking or symptoms of respiratory dysfunction

Other:

Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No active systemic infections, autoimmune disease, or active primary or secondary immunodeficiency