Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Interferon alfa Following Surgery in Treating Patients With Stage III Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 to 70	Other	EORTC-18991 NCT00006249

Objectives

1. 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.
2. Compare the overall survival in these patients after treatment with pegylated interferon alfa vs observation.
3. Determine the toxicity of pegylated interferon alfa in these patients.
4. Determine the compliance of these patients treated with pegylated interferon alfa.
5. Compare the quality of life in these patients after treatment with pegylated interferon alfa vs observation.

Entry Criteria

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

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

Patient Characteristics:

Age:

• 18 to 70

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Platelet count greater than 100,000/mm³
• 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

Expected Enrollment

A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 1.5-2 years.

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.

Bottomley A, Coens C, Suciu S, et al.: Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol 27 (18): 2916-23, 2009.[PUBMED Abstract]

Eggermont AM, Bouwhuis MG, Kruit WH, et al.: Serum concentrations of pegylated interferon alpha-2b in patients with resected stage III melanoma receiving adjuvant pegylated interferon alpha-2b in a randomized phase III trial (EORTC 18991). Cancer Chemother Pharmacol : , 2009.[PUBMED Abstract]

Fusi A, Collette S, Busse A, et al.: Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuvant interferon treatment (EORTC 18991 side study). Eur J Cancer : , 2009.[PUBMED Abstract]

Eggermont AM, Suciu S, Santinami M, et al.: Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet 372 (9633): 117-26, 2008.[PUBMED Abstract]

Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991: long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-8504, 473s, 2007.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Alexander Eggermont, MD, PhD, Study coordinator		Ph: 31-10-439-1911 Email: a.m.m.Eggermont@erasmusmc.nl

Registry Information
Official Title		PEG-Intron Observation after Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial
Trial Start Date		2000-06-20
Registered in ClinicalTrials.gov		NCT00006249
Date Submitted to PDQ		2000-07-28
Information Last Verified		2000-10-16

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