Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00006249
• Other study ID #: EORTC-18991
• Secondary ID: EORTC-18991
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 11, 2000
• Last updated: February 9, 2015
• Start date: June 2000

Study information

• Verified date: February 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1258
• Est. primary completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• pegylated interferon alfa

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Austin and Repatriation Medical Centre	Heidelberg West	Victoria
Australia	David Maddison Clincial Sciences	Newcastle
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Sir Charles Gairdner Hospital, Perth	Perth	Western Australia
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Clinique Notre Dame de Grace	Gosselies
Belgium	U.Z. Gasthuisberg	Leuven
Bulgaria	National Centre of Oncology	Sofia
Croatia	University Hospital Sestre Milosrdnice	Zagreb
Czech Republic	Charles University Hospital	Prague (Praha)
Estonia	North-Estonian Regional Hospital Cancer Centre	Tallinn
France	Centre Hospitalier Universitare d'Amens	Amiens
France	CHR de Besancon - Hopital Saint-Jacques	Besancon
France	Hopital Saint Andre	Bordeaux
France	CHU Ambroise Pare	Boulogne Billancourt
France	CHR de Grenoble - La Tronche	Grenoble
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Leon Berard	Lyon
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Hopital St. Eloi	Montpellier
France	Hopital L'Archet - 2	Nice
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Universitaire	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Rene Huguenin	Saint Cloud
France	Centre Hospitalier Regional et Universitaire de Saint-Etienne	Saint Priest en Jarez
France	Hopitaux Universitaire de Strasbourg	Strasbourg
France	Centre Hospitalier Regional Metz Thionville	Thionville
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif
Germany	Robert Roessle Klinik	Berlin
Germany	Saint Josef Hospital	Bochum 1
Germany	Stadt. Kliniken	Dortmund
Germany	Universitaet Erlangen	Erlangen
Germany	Georg August Universitaet	Goettingen
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Universitaets-Hautklinik Heidelberg	Heidelberg
Germany	Universitaet Leipzig - Chirurgische Klinik und Poliklinik I	Leipzig
Germany	Otto - Von - Guericke - Universitaet Magdeburg	Magdeburg
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg
Israel	Rambam Medical Center	Haifa
Israel	Wolfson Medical Center	Holon
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Ospendale S.M. Annunziata-A.S.DI Firenze	Firenze
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)
Italy	European Institute of Oncology - Chemo Prevention	Milano
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Milano (Milan)
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Naples
Italy	Istituto Regina Elena	Rome
Italy	Universita Degli Studi di Torino	Torino
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus University Medical Center	Rotterdam
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Poland	Great Poland Cancer Center	Poznan
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa	Lisbon
Portugal	Instituto Portugues de Oncologia Centro do Porto, SA	Porto
Slovenia	Institute of Oncology, Ljubljana	Ljubljana
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clinico Universitario	Zaragoza
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Inselspital, Bern	Bern
Switzerland	Ratisches Kantons und Regionalspital	Chur
Switzerland	UniversitaetsSpital	Zurich
Turkey	Vakif Gureba Training Hospital	Istanbul
Turkey	Ege University Medical School	Izmir
United Kingdom	Belfast City Hospital Trust	Belfast	Northern Ireland
United Kingdom	Selly Oak Hospital at University Hospital NHS Trust	Birmingham
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's NHS Trust	Cambridge	England
United Kingdom	Velindre Cancer Center at Velinde Hospital	Cardiff	Wales
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Ninewells Hospital and Medical School	Dundee	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Western Infirmary	Glasgow	Scotland
United Kingdom	Royal Surrey County Hospital	Guildford	England
United Kingdom	Princess Royal Hospital	Hull	England
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Guy's and St. Thomas' Hospitals NHS Trust	London	England
United Kingdom	Royal Free Hospital	London	England
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England
United Kingdom	Newcastle General Hospital	Newcastle Upon Tyne	England
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Weston Park Hospital	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden Hospital	Sutton	England
United Kingdom	Southend NHS Trust Hospital	Westcliff-On-Sea	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Australia,  Belgium,  Bulgaria,  Croatia,  Czech Republic,  Estonia,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Portugal,  Slovenia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (8)

Bottomley A, Coens C, Suciu S, Santinami M, Kruit W, Testori A, Marsden J, Punt C, Salès F, Gore M, Mackie R, Kusic Z, Dummer R, Patel P, Schadendorf D, Spatz A, Keilholz U, Eggermont A. Adjuvant therapy with pegylated interferon alfa-2b versus observatio — View Citation

Bouwhuis MG, Suciu S, Testori A, Kruit WH, Salès F, Patel P, Punt CJ, Santinami M, Spatz A, Ten Hagen TL, Eggermont AM. Phase III trial comparing adjuvant treatment with pegylated interferon Alfa-2b versus observation: prognostic significance of autoantib — View Citation

Eggermont AM, Bouwhuis MG, Kruit WH, Testori A, ten Hagen T, Yver A, Xu C. 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 — View Citation

Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991 phase III trial: Long-term adjuvant pegylated interferon-a2b (PEG-IFN) versus observation in resected stage III melanoma: long-term results at 7.6-years follow-up. [Abstract] J Clin Oncol 29 (Suppl 1

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)

Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, Punt CJ, Salès F, Gore M, Mackie R, Kusic Z, Dummer R, Hauschild A, Musat E, Spatz A, Keilholz U; EORTC Melanoma Group. Adjuvant therapy with pegylated interferon alfa-2b versus observati — View Citation

Eggermont AM, Suciu S, Testori A, Kruit WH, Marsden J, Punt CJ, Santinami M, Salès F, Schadendorf D, Patel P, Dummer R, Robert C, Keilholz U, Yver A, Spatz A. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012 Jan;48(2):218-25. doi: 10.1016/j.ejca.2011.09.028. Epub 2011 Nov 5. — View Citation

Fusi A, Collette S, Busse A, Suciu S, Rietz A, Santinami M, Kruit WH, Testori A, Punt CJ, Dalgleish AG, Spatz A, Eggermont AM, Keilholz U. Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuv — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	quality of life	Quality of life evaluation	from randomization	No
Primary	distant-metastasis free-survival (DMFS)	distant-metastasis free-survival (DMFS) after randomization	from randomization	No
Secondary	survival	duration of survival: time from randomization until death, whatever the cause	from randomization till death	No
Secondary	toxicity	toxicity	from randomization	Yes