Vaccine Therapy in Treating Patients With Metastatic Melanoma

Phase 1

Completed

Conditions: Melanoma (Skin)

Interventions: Biological: QS21
Biological: IFA (incomplete Freund's adjuvant)
Biological: p946
Biological: p946/tet-p
Biological: Tet-p

Registration Number: NCT00003224

Lead Sponsor: University of Virginia

Brief 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 3: p946 plus Tet-p plus QS-21	p946	100 mcg peptide gp100 \[280-288\],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 1: peptide 946 plus QS-21	QS21	100 mcg peptide gp100 \[280-288\] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 2. p946 plus IFA	p946	100 mcg peptide gp100 \[280-288\] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 3: p946 plus Tet-p plus QS-21	QS21	100 mcg peptide gp100 \[280-288\],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 1: peptide 946 plus QS-21	p946	100 mcg peptide gp100 \[280-288\] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 4. p946, Tet-p plus IFA	p946	100 mcg peptide gp100 \[280-288\], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 2. p946 plus IFA	IFA (incomplete Freund's adjuvant)	100 mcg peptide gp100 \[280-288\] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 4. p946, Tet-p plus IFA	IFA (incomplete Freund's adjuvant)	100 mcg peptide gp100 \[280-288\], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 6. p946/Tet-p plus IFA	p946/tet-p	282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 3: p946 plus Tet-p plus QS-21	Tet-p	100 mcg peptide gp100 \[280-288\],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 6. p946/Tet-p plus IFA	IFA (incomplete Freund's adjuvant)	282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 4. p946, Tet-p plus IFA	Tet-p	100 mcg peptide gp100 \[280-288\], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant
Group 5: p946/Tet-p plus QS-21	QS21	282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant
Group 5: p946/Tet-p plus QS-21	p946/tet-p	282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of Each Vaccine Regimen	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.