Pegylated Interferon-alpha-2a in Patients With Malignant Melanoma Stage IIA-IIIB

Randomized, Multicenter, Open Label Study to Compare the Efficacy and Tolerability of Pegylated Interferon-alpha-2 (PEG-IFN) to 'Low-dose' Interferon-alpha-2a in Patients With Malignant Melanoma in Stages IIA (T3a) - IIIB (AJCC 2002)

The purpose of this study is to evaluate the efficacy and safety of adjuvant treatment with pegylated interferon-α-2a (PEG-IFN) vs. 'low dose' interferon-α-2a in patients with malignant melanoma in stage IIA (T3a) - IIIB.

A total of 880 will be randomized up to three months after first surgical management of their melanoma to either: PEG-IFN-α-2a or low-dose interferon-α-2a.

Inclusion Criteria:

• Histologically proven cutaneous melanoma
• ≥ 18 years of age and < 75 years of age
• Have confirmed stage IIa (T3a), IIB, IIC, IIIA or IIIB (AJCC 2002) melanoma (lymph node staging either per sentinel node biopsy or elective lymph node dissection)
• Have a Karnofsky performance status of ≥ 80%
• Negative pregnancy test
• Start of therapy within three months after surgery
• Informed consent

Exclusion Criteria:

• Pregnant or lactating women

• Unwillingness or inability to employ an effective barrier method of birth control throughout the study and for up to 3 months after end of treatment in female or male patients

• Mucous membrane or ocular melanoma

• Any evidence of distant metastasis (CT-scan of brain, Chest X ray or CT, abdominal ultrasound or CT and ultrasound of regional lymph nodes at screening)

• Patients who have received chemotherapy or vaccines for melanoma

• Patients with tumor progression under a previous adjuvant interferon therapy or within three months after termination of interferon therapy (patients previously receiving adjuvant interferon therapy in another tumor stage without disease progression may be included)

• History of any other malignancy within the last ten years (except basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix)

• Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina), severe liver disease or severe renal disease.

• ALAT or ASAT > 2 x ULN

• Bilirubin > 2 x ULN

• Creatinine > 2 x ULN

• Patients who have a history of depression or other psychiatric diseases requiring hospitalisation

• Patients with seizure disorders requiring anticonvulsant therapy

• Any of the following abnormal baseline hematologic/laboratory values:

  • Hb <10g/dl
  • WBC <3.0 x 109 /l
  • Platelets <100x109/l
  • Neutrophils < 1.5 x 109/l

• History or presence of autoimmune disease (i.e. autoimmune hepatitis, thyroid auto-immune dysfunction, systemic lupus erythematodes)

• Unwilling or unable to comply with the requirements of the protocol for the duration of the study

• Known infection with HBV, HCV, HIV

• Evidence of allergy or hypersensitivity against IFN or pegylated interferon

• Thyroid disease poorly controlled on prescribed medications

• Systemic corticosteroid therapy for any reason (>1 month)