Vaccine Therapy in Treating Patients With Metastatic Melanoma

November 18, 2014 updated by: Craig L Slingluff, Jr, University of Virginia

Phase I Protocol for the Evaluation of the Safety and Immunogenicity of Vaccination With a Synthetic Melanoma Peptide in Patients With High Risk Melanoma

RATIONALE: Vaccines made from peptide 946 may make the body build an immune response to kill tumor cells. Combining these vaccines with proteins from the tetanus vaccine, and/or with either QS21 or Montanide ISA-51 may be an effective treatment for metastatic melanoma.

PURPOSE: Randomized phase I trial to study the effectiveness of vaccines made from peptide 946 with or without tetanus peptide, QS21, or Montanide ISA-51 in treating patients with metastatic melanoma that cannot be surgically removed or with melanoma that is likely to recur.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the safety of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma.

II. Determine the immunogenicity of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 6 treatment arms: Arm I: Patients receive peptide 946 melanoma vaccine (peptide 946) emulsified with QS21 subcutaneously (SQ). Arm II: Patients receive peptide 946 emulsified with Montanide ISA-51 (ISA-51) SQ. Arm III: Patients receive peptide 946 combined with tetanus peptide melanoma vaccine (tetanus peptide) emulsified with QS21 SQ. Arm IV: Patients receive peptide 946 combined with tetanus peptide emulsified with ISA-51 SQ. Arm V: Patients receive peptide 946-tetanus peptide conjugate emulsified with QS21 SQ. Arm VI: Patients receive peptide 946-tetanus peptide conjugate emulsified with ISA-51 SQ. Initially, 4 patients are randomized to Arm I and 4 patients are randomized to Arm II. If no dose limiting toxicities are observed in these patients, then additional patients are randomized to arms III-VI. Patients in each arm receive vaccine on day 0 and at months 1, 2, 3, 6, 9, and 12. Patients are followed at 6 and 12 months.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

22

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
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Cancer Center, University of Virginia HSC

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

18 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Histologically confirmed unresectable metastatic melanoma (AJCC stage III or IV) OR resected melanoma with high risk of recurrence or mortality (stage IIB and above)
  • Age: 18 to 79
  • Performance status: ECOG 0-2
  • Life expectancy: Greater than 12 months
  • Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL
  • Hepatic: AST and ALT no greater than 2.5 times upper limit of normal (ULN) Bilirubin no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN
  • Renal: Creatinine no greater than 1.5 times ULN

Exclusion criteria:

  • patients currently receiving cytotoxic chemotherapy or who have received that therapy within the preceding 3 months
  • known or suspected allergies to any component of the treatment vaccine
  • unresectable tumor llikely to cause symptoms and for which therapy is anticipated within 3 months.
  • receiving acute treatment for seriouis infection within 14 days.
  • Patients with bulky disease, or with multiple brain metastases, but solitary brain metastases treated successfully with surgery or gamma knife may be eligible.
  • Any of the following with 3 months:
  • agentes with putative immunomodulating activity (except NSAIDs)
  • allergy desensitizing injections
  • other investigational agents
  • interferons
  • corticosteroids
  • any growth factors
  • prior melanoma vaccinations
  • pregnancy or the possibility of becoming pregnant on study
  • medical contraindication or potential problems in complying with the requirements of the protocol.

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
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Group 1: peptide 946 plus QS-21
100 mcg peptide gp100 [280-288] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Biological: QS21
vaccine adjuvant
Biological: p946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
Other Names:
  • peptide 946, gp100 [280-288], YLEPGPVTA
EXPERIMENTAL: Group 2. p946 plus IFA
100 mcg peptide gp100 [280-288] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Biological: p946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
Other Names:
  • peptide 946, gp100 [280-288], YLEPGPVTA
Biological: IFA (incomplete Freund's adjuvant)
Peptides emulsified in IFA.
Other Names:
  • Montanide ISA-51, from Seppic.
EXPERIMENTAL: Group 3: p946 plus Tet-p plus QS-21
100 mcg peptide gp100 [280-288],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Biological: QS21
vaccine adjuvant
Biological: p946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
Other Names:
  • peptide 946, gp100 [280-288], YLEPGPVTA
Biological: Tet-p
modified form of the p2 peptide from tetanus toxoid, used as nonspecific epitope for helper T cells.
Other Names:
  • tetanus peptide melanoma vaccine
EXPERIMENTAL: Group 4. p946, Tet-p plus IFA
100 mcg peptide gp100 [280-288], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Biological: p946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
Other Names:
  • peptide 946, gp100 [280-288], YLEPGPVTA
Biological: IFA (incomplete Freund's adjuvant)
Peptides emulsified in IFA.
Other Names:
  • Montanide ISA-51, from Seppic.
Biological: Tet-p
modified form of the p2 peptide from tetanus toxoid, used as nonspecific epitope for helper T cells.
Other Names:
  • tetanus peptide melanoma vaccine
EXPERIMENTAL: Group 5: p946/Tet-p plus QS-21
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Biological: QS21
vaccine adjuvant
Biological: p946/tet-p
This peptide is a longer version of p946 (gp100 [280-288]) sythesized colinearly with the tetanus helper peptide (Tet-p)
Other Names:
  • peptide 946-tetanus peptide conjugate melanoma vaccine
EXPERIMENTAL: Group 6. p946/Tet-p plus IFA
282 mcg gp100 [280-288]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Biological: IFA (incomplete Freund's adjuvant)
Peptides emulsified in IFA.
Other Names:
  • Montanide ISA-51, from Seppic.
Biological: p946/tet-p
This peptide is a longer version of p946 (gp100 [280-288]) sythesized colinearly with the tetanus helper peptide (Tet-p)
Other Names:
  • peptide 946-tetanus peptide conjugate melanoma vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety: Grade 3 Adverse Events
Time Frame: Up to 24 months after last vaccine
Adverse events are monitored according to NCI/DCT Common Toxicity Criteria
Up to 24 months after last vaccine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity of Each Vaccine Regimen
Time Frame: up to 12 months since enrollment
T cell responses to the p946 (gp100 [280-288]) peptide. All enrolled patients were assayed for immune response to the gp100 peptide by ELIspot assay after 14 days in vitro sensitization. The number with a response in each study arm is reported.
up to 12 months since enrollment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Proliferative Response to Tetanus Helper Peptide
Time Frame: during vaccination
Proliferative response measured in participants using a tritiated thymidine incorporation assay with peripheral blood mononuclear cells (PBMC) stimulated with the tetanus peptide in vitro, and measured at 5 days after in vitro culture.
during vaccination

Collaborators and Investigators

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

Sponsor

University of Virginia

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

February 1, 1996

Primary Completion (ACTUAL)

August 1, 2000

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

August 24, 2004

First Posted (ESTIMATE)

August 25, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

November 20, 2014

Last Update Submitted That Met QC Criteria

November 18, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6346
  • NCI-H98-0010

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.

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