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
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.
- 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
- Renal: Creatinine no greater than 1.5 times ULN
- 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
- 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