Immunization With 8 Peptides Mixed With Adjuvant Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma

Inclusion Criteria

1. Histologically proven cutaneous melanoma, or clear cell sarcoma, which is considered as a subtype of melanoma.

2. Melanoma must be at one of the following AJCC 2002 stages:

   • Regional metastatic disease (any T; N2b, N2c or N3; M0).
   • Distant metastatic disease (any T; any N; M1a, M1b or M1c), except brain or leptomeningeal localizations, and except elevated LDH.
3. Patients must be HLA-A2.
4. A pre-immune tumor biopsy must be kept frozen for post-study PCR analysis.
5. Presence of at least one measurable or non-measurable tumor lesion.
6. Expected survival of at least 3 months.
7. Karnofsky performance scale ≥70 or WHO performance status of 0 or 1.

8. Within the last 4 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:

   Lab Parameter Range

   • Hemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l
   • Granulocytes ≥ 1,500/µl
   • Lymphocytes ≥ 700/µl
   • Platelets ≥ 100,000/µl
   • Serum creatinin ≤ 2.0 mg/dl or ≤ 177 mmol/l
   • Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 mmol/l
   • ASAT and ALAT ≤ 2 x the normal upper limits
   • LDH ≤ the normal upper limit.

9. Viral tests:

   • HIV (human immunodeficiency virus): negative antibodies.
   • HBV (hepatitis B virus): negative antigens; antibodies may be positive.
   • HCV (hepatitis C virus): negative antibodies.
10. Age ≥ 18 years
11. Able and willing to give valid written informed consent.

Exclusion Criteria

1. Previous treatment with more than one regimen of systemic chemotherapy, combined or not with non-specific immunotherapy such as interferon alpha or interleukins. Chemoimmunotherapy or radiotherapy must be stopped within the preceding 4 weeks (6 weeks for nitrosoureas and mitomycin C).
2. Clinically significant heart disease (NYHA Class III or IV) i.e. NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
3. Active immunodeficiency or autoimmune disease. Vitiligo is not an exclusion criterion.
4. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study.
5. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
6. Lack of availability for immunological and clinical follow-up assessments.
7. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
8. Pregnancy or breastfeeding.
9. Women of childbearing potential: Refusal or inability to use effective means of contraception.