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

Study Overview
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Brief Summary
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RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether treatment with interferon alfa is more effective than observation alone for stage II or stage III melanoma that has been completely removed surgically. PURPOSE: This randomized phase III trial is studying high dose interferon alfa to see how well it works compared to observation only in treating patients with stage II or stage III melanoma that has been completely removed by surgery.

Detailed Description
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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.

Official Title
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Phase III Randomized Study of Four Weeks of High Dose Interferon Alfa-2b in Stage T2bN0, T3a-bN0, T4a-bN0, and T1-4, N1a,2a (Microscopic) Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: interferon alfa-2b
* Other: observation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Observation<br>Patients undergo observation for 4 weeks. | Other: observation<br>* Patients undergo observation for 4 weeks.<br>* Other names: clinical observation;|
| Experimental: Interferon Alfa-2b<br>Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity. | Biological: interferon alfa-2b<br>* Given IV<br>* Other names: NSC # 377523;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year Relapse-free Survival Rate | Relapse-free survival (RFS) was defined as time from randomization to disease relapse or death from any cause, whichever occurred first. Patients without disease relapse were censored at last disease assessment date known of free of relapse. Kaplan-Meier method was used to estimate 5-year RFS rate in the intent-to-treat (ITT) patients. | assessed every 3 months for 2 years, every 6 months for 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year Overall Survival Rate | Overall survival (OS) was defined as time from randomization to death from any cause. Patients still alive were censored at last known alive date. Kaplan-Meier method was used to estimate 5-year OS rate in the ITT patients. | assessed every 3 months for 2 years, every 6 months for 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II melanoma, stage III melanoma