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.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma stage II melanoma stage III melanoma Recurrent Melanoma	Drug: Montanide ISA-51  Drug: Montanide ISA-51/peptide 946 melanoma vaccine  Drug: Montanide ISA-51/peptide 946-tetanus peptide conjugate  Drug: peptide 946 melanoma vaccine  Drug: peptide 946-tetanus peptide conjugate melanoma vaccine  Drug: QS21  Drug: tetanus peptide melanoma vaccine	Phase I

Further Study Details: 

OBJECTIVES: I. Compare the safety and 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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years   -   79 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed unresectable metastatic melanoma (AJCC stage III or IV) OR resected melanoma with high risk of recurrence or mortality (stage IIB and above)
• No multiple visceral metastases greater than 3 cm in diameter
• Solitary brain metastases allowed if less than 2 cm in diameter and successfully treated with surgical excision or gamma knife radiation therapy
• HLA-A2 positive

--Prior/Concurrent Therapy--

• Biologic therapy: At least 3 months since prior interferons; At least 3 months since prior growth factors; No prior melanoma vaccinations; No concurrent interferons; No concurrent growth factors
• Chemotherapy: At least 3 months since prior chemotherapy; No concurrent chemotherapy
• Endocrine therapy: At least 3 months since prior agents with putative immunomodulating activity (except nonsteroidal antiinflammatory drugs); At least 3 months since prior corticosteroids; No concurrent agents with putative immunomodulating activity (except nonsteroidal antiinflammatory drugs); No concurrent corticosteroids
• Radiotherapy: Prior radiotherapy allowed; See Disease Characteristics; No concurrent radiotherapy
• Surgery: Prior surgery allowed; See Disease Characteristics
• Other: At least 3 months since prior allergy desensitization injections; At least 3 months since other prior investigational drugs or therapy; At least 14 days since acute treatment for serious infection; No concurrent allergy desensitization injections; No concurrent investigational drugs or therapy

--Patient Characteristics--

• 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
• Other: No known or suspected allergies to any component of the treatment vaccine; Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception

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

Study chairs or principal investigators

Craig L. Slingluff, Jr.,  Study Chair,  University of Virginia   

Study ID Numbers:  CDR0000066086; UVACC-HIC-6346; NCI-H98-0010; UVA-HIC-6346
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003224
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08