High-Dose or Low-Dose Interferon Alfa Compared With No Further Therapy Following Surgery in Treating Patients With Stage III Melanoma

Melanoma (Skin) Clinical Trial

Official title:

POST-OPERATIVE ADJUVANT INTERFERON-ALFA-2B (INTRON-A) TREATMENT AFTER RESECTION OF THICK PRIMARY MELANOMA AND/OR REGIONAL LYMPHNODE METASTASES 'INTERMEDIATE-HIGH DOSE' VS INTERMEDIATE-LOW DOSE' IFN-ALFA VS OBSERVATION: A 3-ARM MULTICENTER RANDOMIZED PHASE III TRIAL

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00002763
• Other study ID #: CDR0000064718
• Secondary ID: EORTC-18952
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 15, 2011
• Start date: April 1996

Study information

• Verified date: November 2011
• Source: National Cancer Institute (NCI)
• 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 cancer cells. It is not known whether giving high-dose or low-dose interferon alfa is more effective than no further therapy in treating patients with stage III melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of high- or low-dose interferon alfa with that of no further therapy following surgery in treating patients who have stage III melanoma.

Description:

OBJECTIVES: I. Evaluate the time to distant metastasis, death due to melanoma, and overall survival in patients with high-risk stage III melanoma treated with 10 MU of interferon alfa (IFN-A) for 4 weeks followed by 1 year of IFN-A at 10 MU three times per week vs. 2 years of IFN-A at 5 MU three times per week vs. observation alone. II. Assess the toxicity associated with IFN-A. III. Compare the quality of life, costs, and compliance associated with each treatment regimen.

OUTLINE: Randomized study. Following definitive surgical resection, patients are randomly assigned in a 2:2:1 ratio to Arms A, B, and C, respectively. Arm A: Biological Response Modifier Therapy. Interferon alfa-2b (Schering), IFN-A, NSC-377523. Higher dose. Arm B: Biological Response Modifier Therapy. IFN-A. Lower dose. Arm C: Control. Observation.

PROJECTED ACCRUAL: A total of 1,000 patients will be entered over approximately 4 years in this multicenter study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 75 Years

Eligibility

DISEASE CHARACTERISTICS: Cutaneous melanoma in one of the following categories: T4, N0, M0 Deep primary tumor with Breslow depth greater than 4.0 cm Tx, N1, M0 Primary tumor with regional lymph node metastases found at lymphadenectomy but clinically undetectable Tx, N2, M0 Clinically apparent regional lymph node metastases (synchronous or metachronous) confirmed by lymphadenectomy Definitive surgical resection and lymphadenectomy with pathologically confirmed adequate surgical margins required Minimum 2 cm margin for primary lesions with Breslow depth greater than 2 mm Distal interphalangeal amputation required for subungual melanomas No primary melanoma originating apart from the skin No multiple in transit metastases in an extremity No lymph node involvement outside the operative area resected by radical neck, axillary lymph node, or ilioinguinal dissection

PATIENT CHARACTERISTICS: Age: 16 to 75 Performance status: ECOG 0 or 1 Hematopoietic: WBC at least 4,000 Platelets at least 125,000 Hemoglobin at least 9.8 g/dL (6.1 mmol/L) Hepatic: Bilirubin no greater than 2 times normal AST no greater than 2 times normal Renal: Creatinine no greater than 1.6 mg/dL (140 micromoles/L) Cardiovascular: No ventricular or supraventricular arrhythmia requiring treatment No congestive heart failure (NYHA class 3/4 status) Other: No uncontrolled infection No requirement for ongoing steroids, NSAIDs, or other immunomodulators No organic brain syndrome or significant impairment of basal cognitive function No psychiatric disorder that would preclude study participation or would be exacerbated by study therapy (e.g., depression) No second malignancy except: In situ cervical cancer Nonmelanomatous skin cancer No pregnant or nursing women

PRIOR CONCURRENT THERAPY: No prior treatment on this protocol for patients with recurrent melanoma at regional lymph nodes No preoperative infusion or perfusion therapy Biologic therapy: No prior adjuvant immunotherapy Chemotherapy: No prior adjuvant systemic chemotherapy No prior anthracyclines Endocrine therapy: Not specified Radiotherapy: No prior adjuvant radiotherapy Surgery: See Disease Characteristics

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• recombinant interferon alfa

Locations

Country	Name	City	State
Austria	Krankenhaus der Elisabethinen	Linz
Austria	Landeskrankenanstalten - Salzburg	Salzburg
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Ghent (Gent)
Belgium	U.Z. Gasthuisberg	Leuven
Bulgaria	Alexander's University Hospital	Sofia
Bulgaria	National Centre of Oncology	Sofia
Croatia	University Hospital Sestre Milosrdnice	Zagreb
Estonia	Estonian Cancer Center	Tallinn
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
France	CHU de Bordeaux - Hopital Pellegrin	Bordeaux
France	Institut Bergonie	Bordeaux
France	CHU Ambroise Pare	Boulogne Billancourt
France	CHRU de Caen	Caen
France	Centre Leon Berard	Lyon
France	Centre Antoine Lacassagne	Nice
France	Hopital L'Archet - 2	Nice
France	Hopital Bichat-Claude Bernard	Paris
France	Hopital Cochin	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Haut Leveque	Pessac
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	Institut Claudius Regaud	Toulouse
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Institut Gustave Roussy	Villejuif
Germany	Robert Roessle Klinik	Berlin
Germany	Universitaetsklinikum Benjamin Franklin	Berlin
Germany	Universitaets-Augenklinik - Erlangen	Erlangen
Germany	Georg August Universitaet	Goettingen
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Universitats-Krankenhaus Eppendorf	Hamburg
Germany	Department of Dematology, Hannover Medical School	Hannover
Germany	Universitaets-Hautklinik Heidelberg	Heidelberg
Germany	Universitatsklinik, Saarland	Homburg/Saar
Germany	III Medizinische Klinik Mannheim	Mannheim
Germany	Klinikum der Universitat Regensburg	Regensburg
Germany	Universitatshautklinik Eberhard - Karlsuniversitat Tubingen	Tubingen
Germany	Department of Dermatology	Ulm
Germany	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg
Israel	Wolfson Medical Center	Holon
Israel	Tel-Aviv Medical Center-Ichilov Hospital	Tel-Aviv
Italy	Istituto Europeo Di Oncologia	Milano
Netherlands	Academisch Ziekenhuis der Vrije Universiteit	Amsterdam
Netherlands	Antoni van Leeuwenhoekhuis	Amsterdam
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Rotterdam Cancer Institute	Rotterdam
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Poland	Medical University of Gdansk	Gdansk
Poland	Maria Sklodowska-Curie M.C.C.I.O. Krakow	Krakow (Cracow)
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Portugal	Instituto Portugues de Oncologia de Francisco Gentil	Lisbon
Portugal	Instituto Portugues de Oncologia do Porto	Porto
Russian Federation	Russian Academy of Medical Sciences Cancer Research Center	Moscow
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Hospital Clinic y Provincial de Barcelona	Barcelona
Spain	Hospital Clinico Universitario	Zaragoza
Sweden	Huddinge Hospital	Huddinge
Switzerland	Ospedale San Giovanni	Bellinzona
Switzerland	Inselspital, Bern	Bern
Switzerland	Ratisches Kantons und Regionalspital	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital - Saint Gallen	Saint Gallen
Switzerland	Universitaetsspital	Zurich
Turkey	Cukurova University School of Medicine	Adana
Turkey	Cerrahpasa Medical School	Istanbul
Turkey	Istanbul University-Institute of Oncology	Istanbul
Turkey	Vakif Gureba Training Hospital	Istanbul
Turkey	Ege University Medical School	Izmir
United Kingdom	Bristol Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's NHS Trust	Cambridge	England
United Kingdom	Beatson Oncology Centre	Glasgow	Scotland
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Derriford Hospital	Plymouth	England

Sponsors (1)

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

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Croatia,  Estonia,  Finland,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Portugal,  Russian Federation,  Serbia,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (8)

Bouwhuis M, Suciu S, Kruit W, et al.: Prognostic value of autoantibodies (auto-AB) in melanoma patients (pts) in the EORTC 18952 trial of adjuvant interferon (IFN) compared to observation (obs). [Abstract] J Clin Oncol 25 (Suppl 18): A-8507, 473s, 2007.

Bouwhuis MG, Collette S, Suciu S, de Groot ER, Kruit WH, Ten Hagen TL, Aarden LA, Eggermont AM, Swaak AJ; EORTC Melanoma Group. Changes of ferritin and CRP levels in melanoma patients treated with adjuvant interferon-a (EORTC 18952) and prognostic value o — View Citation

Bouwhuis MG, Suciu S, Collette S, Aamdal S, Kruit WH, Bastholt L, Stierner U, Salès F, Patel P, Punt CJ, Hernberg M, Spatz A, ten Hagen TL, Hansson J, Eggermont AM; EORTC Melanoma Group and the Nordic Melanoma Group. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon. J Natl Cancer Inst. 2009 Jun 16;101(12):869-77. doi: 10.1093/jnci/djp132. Epub 2009 Jun 9. — View Citation

Bouwhuis MG, Suciu S, Kruit W, Salès F, Stoitchkov K, Patel P, Cocquyt V, Thomas J, Liénard D, Eggermont AM, Ghanem G; European Organisation for Research and Treatment of Cancer Melanoma Group. Prognostic value of serial blood S100B determinations in stag — View Citation

Eggermont AM, Punt CJ. Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival? Am J Clin Dermatol. 2003;4(8):531-6. Review. — View Citation

Eggermont AM, Suciu S, MacKie R, Ruka W, Testori A, Kruit W, Punt CJ, Delauney M, Sales F, Groenewegen G, Ruiter DJ, Jagiello I, Stoitchkov K, Keilholz U, Lienard D; EORTC Melanoma Group. Post-surgery adjuvant therapy with intermediate doses of interferon — 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

Suciu S, Ghanem G, Kruit W, et al.: Serum S-100B protein is a strong independent prognostic marker for distant-metastasis free survival (DMFS) in stage III melanoma patients: an evaluation of the EORTC randomized trial 18952 comparing IFNa versus observat