High-Dose Interferon Alfa in Treating Patients With Stage II or Stage III Melanoma

OBJECTIVES:

Primary Objective:

• Compare the effect of high-dose interferon alfa-2b treatment on the relapse-free survival of patients with stage II or III resected malignant melanoma.

Secondary Objectives:

• Compare the effect of this treatment regimen on overall survival of these patients.
• Assess the toxicity of this treatment in these patients.
• Compare the effect of treatment on quality of life.

OUTLINE: This is a randomized study. Patients are stratified by pathologic lymph node status (known vs unknown),lymph node staging procedures(sentinel lymph node procedure vs. elective lymph node dissection vs. no lymphadenectomy), Breslow depth (<= 1.0 mm vs. 1.01-2.0 mm vs. 2.01-4.0 mm vs > 4.0 mm), ulceration of the primary lesion (yes vs. no vs. unknown), and disease stage (lymph node positive [N1, N2a] vs. lymph node negative [N0]). Patients are randomized into one of two treatment arms in a 1:1 ratio.

• Arm I (observation): Patients undergo observation for 4 weeks.
• Arm II (Interferon Alfa-2b): Patients receive high-dose interferon alfa-2b intravenously (IV) over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.

Quality of life is assessed before treatment, at day 22, every 3 months for 2 years, and then every 6 months for 3 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter until 15 years after randomization.

PROJECTED ACCRUAL: A total of 1,420 patients will be accrued for this study over 5 years.

Inclusion criteria

• Histologically confirmed primary melanoma of cutaneous origin

• Stage II (T3 N0 M0 1.5-4.0 mm Breslow depth)

• Clinically negative regional lymph node pathologic status unknown OR
• Histologically negative regional lymph nodes
• Stage III (T4 N0 M0)

• Greater than 4.0 mm Breslow depth OR
• Stage III (T1-4 N1)

• One lymph node positive microscopically
• Patients must meet at least 1 of the following criteria:

• T2b N0 - primary melanoma 1.01-2.0 mm with ulceration, node negative
• T3a-b N0 - primary melanoma 2.01-4.0 mm with and without ulceration, node negative
• T4a-b N0 - primary melanoma > 4.0 mm with or without ulceration, node negative
• T1a N1a-2a (microscopic) - primary melanoma of any thickness with microscopically positive lymph node (any number)
• Patients with a positive sentinel node should undergo complete lymphadenectomy of the nodal basin prior to study
• Must complete all primary therapy (wide excision with or without lymphadenectomy) and be randomized in this study within 84 days of wide excision
• Must have undergone an adequate wide excision of the primary lesion
• Age 18 and over (For ECOG patients only, patients must be >=10 years)
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
• Adequate hematopoietic, hepatic, and renal function based on the following tests:

• White blood cell (WBC) cout at least 3,000/mm^3
• Platelet count at least 125,000/mm^3
• Hematocrit at least 30%
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase no greater than 2 times ULN
• If lactate dehydrogenase or alkaline phosphatase is above normal, a contrast-enhanced computed tomography (CT) scan or Magnetic resonance imaging (MRI) of the liver is required to document the absence of tumor
• Blood urea nitrogen (BUN) no greater than 33 mg/dL OR Creatinine no greater than 1.8 mg/dL
• No other concurrent or prior malignancies within the past 5 years except:

• Cancer in situ
• Lobular carcinoma in situ of the breast
• Carcinoma in situ of the cervix
• Atypical melanocytic hyperplasia or Clark 1 melanoma in situ
• Basal or squamous cell skin cancer
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study

Exclusion criteria

• Clinical, radiological/laboratory, or pathological evidence of incompletely resected melanoma or any distant metastatic disease
• Clinically palpable lymphadenopathy
• Evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that would preclude study participation
• Other significant medical or surgical condition, or any medication or treatment regimens, that would interfere with study participation
• Pregnant or nursing
• Other history of invasive melanoma
• Autoimmune disorders or conditions of immunosuppression
• History of active ischemic heart disease
• Cerebrovascular disease
• Congestive heart failure (New York Heart Association class III or IV heart disease)
• Prior or concurrent chemotherapy
• Prior immunotherapy including tumor vaccines, interferon, interleukins, levamisole, or other biologic response modifiers for melanoma
• Concurrent systemic corticosteroids including oral steroids (i.e., prednisone, dexamethasone), topical steroid creams or ointments, or any steroid-containing inhalers
• Prior or concurrent radiotherapy
• Other concurrent immunosuppressive medications