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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00002763

Collaborator

(none)

1,000

Enrollment

Locations

11.6

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: recombinant interferon alfa	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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

Study Start Date :

Apr 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus der Elisabethinen	Linz		Austria	4020
2	Landeskrankenanstalten - Salzburg	Salzburg		Austria	5020
3	Institut Jules Bordet	Brussels (Bruxelles)		Belgium	1000
4	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)		Belgium	1200
5	Hopital Universitaire Erasme	Brussels		Belgium	1070
6	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi		Belgium	6000
7	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
8	Universitair Ziekenhuis Gent	Ghent (Gent)		Belgium	B-9000
9	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
10	Alexander's University Hospital	Sofia		Bulgaria	1431
11	National Centre of Oncology	Sofia		Bulgaria	1756
12	University Hospital Sestre Milosrdnice	Zagreb		Croatia	10000
13	Estonian Cancer Center	Tallinn		Estonia	11619
14	Tampere University Hospital	Tampere		Finland	33521
15	Turku University Central Hospital	Turku		Finland	FIN-2-0521
16	CHU de Bordeaux - Hopital Pellegrin	Bordeaux		France	33076
17	Institut Bergonie	Bordeaux		France	33076
18	CHU Ambroise Pare	Boulogne Billancourt		France	F-92104
19	CHRU de Caen	Caen		France	14033
20	Centre Leon Berard	Lyon		France	69373
21	Centre Antoine Lacassagne	Nice		France	06189
22	Hopital L'Archet - 2	Nice		France	F-06202
23	Hopital Bichat-Claude Bernard	Paris		France	75018
24	Hopital Saint-Louis	Paris		France	75475
25	Hopital Cochin	Paris		France	75674
26	Hopital Haut Leveque	Pessac		France	33604
27	Centre Eugene Marquis	Rennes		France	35062
28	Centre Rene Huguenin	Saint Cloud		France	92210
29	Centre Hospitalier Regional et Universitaire de Saint-Etienne	Saint Priest en Jarez		France	42277
30	Hopitaux Universitaire de Strasbourg	Strasbourg		France	67091
31	Centre Hospitalier Regional Metz Thionville	Thionville		France	57126
32	Institut Claudius Regaud	Toulouse		France	31052
33	Centre Hospitalier Universitaire Bretonneau de Tours	Tours		France	37044
34	Institut Gustave Roussy	Villejuif		France	F-94805
35	Universitaetsklinikum Benjamin Franklin	Berlin		Germany	D-12200
36	Robert Roessle Klinik	Berlin		Germany	D-13122
37	Universitaets-Augenklinik - Erlangen	Erlangen		Germany	D-91054
38	Georg August Universitaet	Goettingen		Germany	D-37075
39	Universitats-Krankenhaus Eppendorf	Hamburg		Germany	D-20246
40	Haematologisch-Onkologische Praxis Altona	Hamburg		Germany	D-22765
41	Department of Dematology, Hannover Medical School	Hannover		Germany	D-30449
42	Universitaets-Hautklinik Heidelberg	Heidelberg		Germany	D-69115
43	Universitatsklinik, Saarland	Homburg/Saar		Germany	D-66421
44	III Medizinische Klinik Mannheim	Mannheim		Germany	D-68305
45	Klinikum der Universitat Regensburg	Regensburg		Germany	DOH-9-3053
46	Universitatshautklinik Eberhard - Karlsuniversitat Tubingen	Tubingen		Germany	DOH-7-2076
47	Department of Dermatology	Ulm		Germany	DOH-8-9081
48	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg		Germany	D-97080
49	Wolfson Medical Center	Holon		Israel	58100
50	Tel-Aviv Medical Center-Ichilov Hospital	Tel-Aviv		Israel	62995
51	Istituto Europeo Di Oncologia	Milano		Italy	20141
52	Academisch Ziekenhuis der Vrije Universiteit	Amsterdam		Netherlands	1007 MB
53	Antoni van Leeuwenhoekhuis	Amsterdam		Netherlands	1066 CX
54	Academisch Ziekenhuis Groningen	Groningen		Netherlands	9713 EZ
55	Leiden University Medical Center	Leiden		Netherlands	2300 ZA
56	University Medical Center Nijmegen	Nijmegen		Netherlands	NL-6252 HB
57	Rotterdam Cancer Institute	Rotterdam		Netherlands	3075 EA
58	Academisch Ziekenhuis Utrecht	Utrecht		Netherlands	3508 GA
59	Medical University of Gdansk	Gdansk		Poland	80-211
60	Maria Sklodowska-Curie M.C.C.I.O. Krakow	Krakow (Cracow)		Poland	31-115
61	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw		Poland	02-781
62	Instituto Portugues de Oncologia de Francisco Gentil	Lisbon		Portugal	1093
63	Instituto Portugues de Oncologia do Porto	Porto		Portugal	4200
64	Russian Academy of Medical Sciences Cancer Research Center	Moscow		Russian Federation	115478
65	Institute of Oncology and Radiology of Serbia	Belgrade		Serbia	11000
66	National Cancer Institute - Bratislava	Bratislava		Slovakia	833 10
67	Hospital Clinic y Provincial de Barcelona	Barcelona		Spain	08036
68	Hospital Clinico Universitario	Zaragoza		Spain	50009
69	Huddinge Hospital	Huddinge		Sweden	S-141 86
70	Ospedale San Giovanni	Bellinzona		Switzerland	CH-6500
71	Inselspital, Bern	Bern		Switzerland	CH-3010
72	Ratisches Kantons und Regionalspital	Chur		Switzerland	CH-7000
73	Centre Hospitalier Universitaire Vaudois	Lausanne		Switzerland	CH-1011
74	Kantonsspital - Saint Gallen	Saint Gallen		Switzerland	CH-9007
75	Universitaetsspital	Zurich		Switzerland	CH-8091
76	Cukurova University School of Medicine	Adana		Turkey	01330
77	Vakif Gureba Training Hospital	Istanbul		Turkey	34296
78	Istanbul University-Institute of Oncology	Istanbul		Turkey	34390
79	Cerrahpasa Medical School	Istanbul		Turkey
80	Ege University Medical School	Izmir		Turkey	35220
81	Bristol Oncology Centre	Bristol	England	United Kingdom	BS2 8ED
82	Addenbrooke's NHS Trust	Cambridge	England	United Kingdom	CB2 2QQ
83	St. James's Hospital	Leeds	England	United Kingdom	LS9 7TF
84	Royal Marsden NHS Trust	London	England	United Kingdom	SW3 6JJ
85	Derriford Hospital	Plymouth	England	United Kingdom	PL6 8DH
86	Beatson Oncology Centre	Glasgow	Scotland	United Kingdom	G11 6NT