Monoclonal Antibody and Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Has Been Removed During Surgery

May 20, 2014 updated by: University of Southern California

An Open-label Study Of MDX-CTLA4 In Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 In The Treatment Of Patients With Resected Stage III Or Stage IV Melanoma

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining monoclonal antibody therapy and vaccine therapy in treating patients who have stage III or stage IV melanoma that has been removed during surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the safety and adverse event profile of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody combined with tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 in patients with resected stage III or IV melanoma.
  • Determine if this regimen causes antigen-specific T-cell activation in these patients.
  • Determine the clearance profile of this regimen in these patients.
  • Assess the development of host immune response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

Patients receive tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 subcutaneously followed by MDX-CTLA4 IV over 90 minutes at 0, 1, 2, 3, 4, 5, 8, and 11 months in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose is determined.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed completely resected stage III or IV melanoma

    • Mucosal or ocular subtypes allowed
  • HLA-A2 positive
  • Positive staining of tumor tissue with antibody HMB-45 for gp100, tyrosinase, and/or MART-1
  • Failed (or ineligible for or refusal of) interferon alfa

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • At least 12 months

Hematopoietic:

  • WBC at least 2,500/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL
  • Hematocrit at least 30%

Hepatic:

  • Bilirubin no greater than upper limit of normal (ULN)
  • AST no greater than 1.25 times ULN
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody nonreactive

Renal:

  • Creatinine less than 1.25 times ULN

Immunologic:

  • Antinuclear antibody (ANA) negative OR

  • If ANA positive, must be:

    • Antithyroglobulin antibody negative
    • Rheumatoid factor negative
    • Anti-LKM antibody negative
    • Anti-phospholipid antibody negative
    • Anti-islet cell antibody negative
    • Anti-neutrophil cytoplasmic antibody negative
  • HIV negative
  • No autoimmune disease (e.g., uveitis or autoimmune inflammatory eye disease)
  • No active infection
  • No hypersensitivity to tyrosinase:368-376, gp100:209-217, MART-1:26-35, or Montanide ISA-51

Other:

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  • No underlying medical condition that would preclude study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • No prior tyrosinase, gp100, or MART-1 peptide
  • No prior antitumor vaccination
  • No prior interleukin-2
  • At least 4 weeks since prior immunotherapy for melanoma

Chemotherapy:

  • At least 4 weeks since prior chemotherapy for melanoma

Endocrine therapy:

  • At least 4 weeks since prior hormonal therapy for melanoma
  • At least 4 weeks since prior corticosteroids
  • No concurrent systemic or topical corticosteroids

Radiotherapy:

  • At least 4 weeks since prior radiotherapy for melanoma

Surgery:

  • See Disease Characteristics

Other:

  • No prior cytotoxic therapy
  • At least 4 weeks since any other prior therapy for melanoma
  • Concurrent analgesics allowed if on stable dose for at least 2 weeks before study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2001

Primary Completion (Actual)

January 1, 2003

Study Completion (Actual)

June 1, 2005

Study Registration Dates

First Submitted

October 11, 2001

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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068934 (10M-00-4)
  • LAC-USC-10M004
  • MDX-MDXCTLA4-03
  • NCI-4210

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Intraocular Melanoma

Clinical Trials on adjuvant therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uruguay

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe