Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma

Study Overview
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Brief Summary
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RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma.

Detailed Description
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OBJECTIVES: Compare the effect of adjuvant therapy with pegylated interferon alfa vs observation, in terms of distant metastases-free survival, in patients with previously resected stage III melanoma. Compare the overall survival in these patients after treatment with pegylated interferon alfa vs observation. Determine the toxicity of pegylated interferon alfa in these patients. Determine the compliance of these patients treated with pegylated interferon alfa. Compare the quality of life in these patients after treatment with pegylated interferon alfa vs observation. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of nodal involvement (N1 vs N2), number of positive nodes (1 vs 2-4 vs 5 or more vs not assessed), Breslow primary (T1-2 vs T3 vs T4 vs unknown), ulceration of primary tumor (absent vs present vs unknown), sex, and center. Patients are randomized to one of two treatment arms. Arm I: Patients receive pegylated interferon alfa subcutaneously weekly for 5 years. Arm II: Patients undergo observation only. Treatment continues in the absence of distant metastases or unacceptable toxicity. Quality of life is assessed at baseline, and then at months 3, 12, 24, 36, 48, and 60. Patients are followed every 6 months for 5 years. PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 1.5-2 years.

Official Title
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PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: pegylated interferon alfa
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed previously resected stage III primary cutaneous melanoma or unknown primary with regional lymph node involvement N1 disease Microscopic, nonpalpable nodal involvement Primary melanoma of any stage with clinically inapparent N1 regional lymph node metastases (T1-4, N1, M0) detected by elective lymph node dissection or sentinel node biopsy N2 disease Palpable nodal involvement with synchronous primary melanoma or apparent nodal disease after prior excision (any pT, N2, M0) Regional lymph node recurrence at any interval after surgery for primary melanoma of any depth (T1-4, rN2, M0) Complete resection of primary melanoma with adequate surgical margins Full lymphadenectomy must be performed within 70 days of study No mucous membrane melanoma or ocular melanoma No evidence of distant or nonregional lymph node metastases or in transit metastases (even if previously resected) No incompletely resected disease due to gross extracapsular extension PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: SGOT and SGPT less than 2 times upper limit of normal No active hepatitis Renal: Creatinine less than 2.0 mg/dL Cardiovascular: No severe cardiovascular disease including the following: Arrhythmias requiring chronic treatment Congestive heart failure (New York Heart Association class III or IV) Symptomatic ischemic heart disease Other: No other prior malignancy within the past 5 years except surgically cured nonmelanomatous skin cancer or carcinoma in situ of the cervix No thyroid dysfunction unresponsive to therapy No uncontrolled diabetes mellitus No active autoimmune disease No active and/or uncontrolled infection No history of neuropsychiatric disorder requiring hospitalization No known active alcohol or drug abuse HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior interferon alfa No prior immunotherapy for melanoma No other concurrent immunologic or biologic therapy No concurrent colony stimulating factors including epoetin alfa and filgrastim (G-CSF) Chemotherapy: No prior chemotherapy for melanoma No concurrent chemotherapy Endocrine therapy: No prior hormonal therapy for melanoma No concurrent hormonal therapy No concurrent chronic systemic corticosteroid therapy Radiotherapy: No prior radiotherapy for melanoma No concurrent radiotherapy Surgery: See Disease Characteristics Recovered from any prior recent surgery Other: At least 30 days since other prior experimental therapy No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| No Intervention: observation<br>5 years observation + 5 years follow up | |
| Experimental: pegylated interferon alfa<br>5 years pegylated interferon alfa + 5 years follow up | Biological: pegylated interferon alfa<br> <br> Procedure: adjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| distant-metastasis free-survival (DMFS) | distant-metastasis free-survival (DMFS) after randomization | from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | duration of survival: time from randomization until death, whatever the cause | from randomization till death | 
| toxicity | toxicity | from randomization | 

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