Vaccine Therapy in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Melanoma (Skin)

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Grade 3 Adverse Events | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma