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