Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With Melanoma

A Phase II Randomized Trial of a Vaccine Combining Tyrosinase/GP100/MART-1 Peptides Emulsified With Montanide ISA 51 With Interleukin-12 With Alum or GM-CSF for Patients With Resected Stages IIB/C, III and IV Melanoma

RATIONALE: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Study Overview

• Status: Completed
• Conditions: Intraocular Melanoma; Melanoma (Skin)
• Intervention / Treatment: Procedure: adjuvant therapy; Biological: recombinant interleukin-12; Biological: gp100 antigen; Biological: incomplete Freund's adjuvant; Biological: tyrosinase peptide; Biological: sargramostim; Biological: MART-1 antigen; Drug: alum adjuvant

Detailed Description

OBJECTIVES:

• Compare the immune reactivity in patients with resected stage IIB, IIC, III, or IV melanoma vaccinated with tyrosinase, gp100, and MART-1 peptides emulsified with Montanide ISA-51 with interleukin-12 and either alum adjuvant or sargramostim (GM-CSF).

OUTLINE: This is a randomized study. Patients are stratified according to disease stage (cutaneous stage IIB, IIC, III, and IV vs ocular and mucosal stage III and IV). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive vaccine with tyrosinase:368-376 (370D)/gp100:209-217 (210M)/MART-1:26-27 (27L) peptides emulsified with Montanide ISA-51 (ISA-51), low-dose interleukin-12 (IL-12) subcutaneously (SC), and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
• Arm II: Patients receive peptide vaccine emulsified with ISA-51, high-dose IL-12 SC, and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
• Arm III: Patients receive peptide vaccine emulsified with ISA-51 on day 1 and low-dose IL-12 SC and sargramostim (GM-CSF) SC on days 1-5 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (20 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • USC/Norris Comprehensive Cancer Center and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of stage IIB, IIC, III, or IV cutaneous melanoma OR stage III or IV ocular or mucosal melanoma

  • Resected or rendered disease-free
• HLA-A2.1-positive by standard cytotoxicity assay

• Tumor tissue must be available for analysis of gp100 staining and tyrosinase and MART-1 expression by immunohistochemistry

  • Must be positive for at least 1 antigen
• Failed, ineligible for, or refused prior interferon alfa

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL
• No bleeding disorder

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT/SGPT no greater than 2.5 times normal
• No coagulation disorder
• Hepatitis surface antigen B negative
• Hepatitis C negative

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No major cardiovascular illness

Pulmonary:

• No major respiratory illness

Immunologic:

• No prior uveitis
• No prior autoimmune inflammatory eye disease
• No immune hemolytic anemia
• No other active autoimmune disease

Other:

• HIV negative
• No major gastrointestinal illness
• No other malignancy within the past 5 years except squamous cell skin cancer or carcinoma in situ of the cervix curatively treated at least 30 days ago
• No major systemic infection (e.g., pneumonia or sepsis)
• No other major medical illness
• No prior allergic reaction to Montanide ISA-51 or alum adjuvant
• No requirement for steroid therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior tyrosinase:368-376 (370D), gp100:209-217 (210M), or MART-1:26-35 (27L) peptides

Chemotherapy:

• At least 1 month since prior adjuvant chemotherapy for this disease
• No concurrent adjuvant chemotherapy

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• At least 1 month since prior radiotherapy for this disease
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 1 month since other prior therapy, including adjuvant therapy, for this disease
• No other concurrent therapy, including adjuvant therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jeffrey S. Weber, MD, PhD, University of Southern California

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: March 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 22, 2014
• Last Update Submitted That Met QC Criteria: May 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; ciliary body and choroid melanoma, medium/large size; extraocular extension melanoma; iris melanoma; recurrent intraocular melanoma; ciliary body and choroid melanoma, small size; 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Gastrointestinal Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Antacids; Interleukin-12; Sargramostim; Aluminum Hydroxide; Freund's Adjuvant; Aluminum sulfate
• Other Study ID Numbers: CDR0000069220 (10M-01-1); LAC-USC-10M011; LAC-USC-IRB-013030; NCI-5506