Patients with an ulcerated melanoma with Breslow >1 mm, N0M0 have a significantly higher risk for relapse than patients with a non-ulcerated primary and about a 40-50% chance of developing stage IV disease to which they will almost invariably succumb. In stage I and II patients with an ulcerated primary who have been sentinel node (SN-staged) and found to be SN-negative there is still a 25-30% relapse risk.

The purpose of this study is to evaluate the effectiveness and safety when treated with PEG IFN alfa-2b for 2 years as compared to observation (no treatment), administered after adequate surgery has been performed for ulcerated primary cutaneous melanomas.

Inclusion Criteria:

• Subjects must be between 18-70 years old.
• Subjects must have histologically documented ulcerated primary cutaneous melanomas with T(2-4)b N0M0.

Adequate resection of ulcerated primary cutaneous melanoma. 1 to 2 cm normal tissue excision margins according to Breslow thickness are recommended. In the head and neck areas and in case of locations distally on extremities, narrower margins are acceptable as long as they are radical (see Appendix F). Subjects must have recovered from the effects of recent surgery.

• SNB must occur within 12 weeks prior randomization.

• Subjects must have an ECOG performance status of 0 or 1 (See Appendix B).

• Subjects must have adequate bone marrow, renal and hepatic function as defined by the following parameters obtained up to maximum 12 weeks prior to randomization:

  • Hematology:
  • WBC >= 3.0 x 109/L
  • Neutrophils > 1.5 x 109/L
  • Platelets > 100 x 109/L
  • Hemoglobin >= 9 g/dL or 5.6 mmol/L
  • Adequate Renal and Hepatic function:
  • Serum creatinine < 2.0 mg/dL or < 140 µmol/L
  • SGOT and SGPT < 2 times upper normal limit of laboratory normal (ULN)

Exclusion Criteria:

• No mucosal melanoma nor ocular melanoma.
• No evidence of nodal involvement confirmed by sentinel lymph node biopsy (SNB). Sentinel Node staging after the excision of the primary must be done between the date of final excision of the primary and the date of randomization.
• No evidence of regional nor distant lymph node metastases nor satellites/in-transit metastases (even if they have been resected).
• No evidence of distant metastasis on clinical examination, CT/MRI of full chest, abdomen and pelvis. Neck CT/MRI if head and neck primary.
• No clinical evidence of brain metastasis.
• No pregnant women
• No breast feeding women
• No patients with a medical condition requiring chronic systemic corticosteroids are not eligible.
• No experimental therapy within 30 days prior to randomization in this study.
• No prior chemotherapy, immunotherapy/vaccine, hormonal or radiation therapy for melanoma.
• No prior treatment with interferon-alfa for any reason.
• No history of prior malignancy within the past 5 years other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ.
• No severe cardiovascular disease, i.e. arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) nor symptomatic ischemic heart disease.
• No thyroid dysfunction not responsive to therapy.
• No poorly controlled (HBA1C>8%) diabetes mellitus or uncontrolled diabetes mellitus, i.e. elevated fasting serum glucose should be < 110% ULN).
• No active autoimmune disease.
• No active and/or uncontrolled infection, including active hepatitis.
• No history of seropositivity for HIV.
• No history of neuropsychiatric disorder requiring hospitalization.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.