Vaccine Therapy in Treating Patients With Metastatic Melanoma

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003224
• Other study ID #: 6346
• Secondary ID: NCI-H98-0010
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: November 18, 2014
• Start date: February 1996

Study information

• Verified date: November 2014
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. primary completion date: August 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• QS21
vaccine adjuvant
• IFA (incomplete Freund's adjuvant)
Peptides emulsified in IFA.
• p946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
• p946/tet-p
This peptide is a longer version of p946 (gp100 [280-288]) sythesized colinearly with the tetanus helper peptide (Tet-p)
• Tet-p
modified form of the p2 peptide from tetanus toxoid, used as nonspecific epitope for helper T cells.

Locations

Country	Name	City	State
United States	Cancer Center, University of Virginia HSC	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, Kittlesen D, Deacon D, Hibbitts S, Grosh WW, Petroni G, Cohen R, Wiernasz C, Patterson JW, Conway BP, Ross WG. Phase I trial of a melanoma vaccine with gp100(280-288) peptide a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With a Proliferative Response to Tetanus Helper Peptide	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	No
Primary	Safety: Grade 3 Adverse Events	Adverse events are monitored according to NCI/DCT Common Toxicity Criteria	Up to 24 months after last vaccine	Yes
Secondary	Immunogenicity of Each Vaccine Regimen	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	No