Interferon Alfa 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: NCT00006249
• Collaborator: (none)
• Enrollment: 1,258
• Locations: 104
• Arms: 2
• Patients Per Site: 12.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: pegylated interferon alfa; Procedure: adjuvant therapy	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1258 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial
• Study Start Date: Jun 1, 2000
• Actual Primary Completion Date: Aug 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: observation 5 years observation + 5 years follow up
Experimental: pegylated interferon alfa 5 years pegylated interferon alfa + 5 years follow up	Biological: pegylated interferon alfa; Procedure: adjuvant therapy

Outcome Measures

Primary Outcome Measures

1. distant-metastasis free-survival (DMFS) [from randomization]

   distant-metastasis free-survival (DMFS) after randomization

Secondary Outcome Measures

1. survival [from randomization till death]

   duration of survival: time from randomization until death, whatever the cause

2. toxicity [from randomization]

   toxicity

Other Outcome Measures

1. quality of life [from randomization]

   Quality of life evaluation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peter MacCallum Cancer Institute	East Melbourne	Victoria	Australia	8006
2	Austin and Repatriation Medical Centre	Heidelberg West	Victoria	Australia	3081
3	Royal Perth Hospital	Perth	Western Australia	Australia	6000
4	Sir Charles Gairdner Hospital, Perth	Perth	Western Australia	Australia	6009
5	David Maddison Clincial Sciences	Newcastle		Australia	NSW 2300
6	Institut Jules Bordet	Brussels		Belgium	1000
7	Hopital Universitaire Erasme	Brussels		Belgium	1070
8	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
9	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
10	Clinique Notre Dame de Grace	Gosselies		Belgium	6041
11	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
12	National Centre of Oncology	Sofia		Bulgaria	1756
13	University Hospital Sestre Milosrdnice	Zagreb		Croatia	10000
14	Charles University Hospital	Prague (Praha)		Czech Republic	128 08
15	North-Estonian Regional Hospital Cancer Centre	Tallinn		Estonia	11619
16	Centre Hospitalier Universitare d'Amens	Amiens		France	80054
17	CHR de Besancon - Hopital Saint-Jacques	Besancon		France	25030
18	Hopital Saint Andre	Bordeaux		France	33075
19	CHU Ambroise Pare	Boulogne Billancourt		France	F-92104
20	CHR de Grenoble - La Tronche	Grenoble		France	38043
21	Centre Hospitalier Regional et Universitaire de Lille	Lille		France	59037
22	Centre Hospital Regional Universitaire de Limoges	Limoges		France	87042
23	Centre Leon Berard	Lyon		France	69373
24	Hopital St. Eloi	Montpellier		France	34295
25	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier		France	34298
26	Hopital L'Archet - 2	Nice		France	F-06202
27	Hopital Bichat - Claude Bernard	Paris		France	75018
28	Hopital Saint-Louis	Paris		France	75475
29	Hopital Haut Leveque	Pessac		France	33604
30	Centre Hospitalier Universitaire	Reims		France	51092
31	Centre Eugene Marquis	Rennes		France	35042
32	Centre Rene Huguenin	Saint Cloud		France	92211
33	Centre Hospitalier Regional et Universitaire de Saint-Etienne	Saint Priest en Jarez		France	42277
34	Hopitaux Universitaire de Strasbourg	Strasbourg		France	67091
35	Centre Hospitalier Regional Metz Thionville	Thionville		France	57126
36	Centre Hospitalier Universitaire Bretonneau de Tours	Tours		France	37044
37	Centre Alexis Vautrin	Vandoeuvre-les-Nancy		France	54511
38	Institut Gustave Roussy	Villejuif		France	F-94805
39	Robert Roessle Klinik	Berlin		Germany	D-13122
40	Saint Josef Hospital	Bochum 1		Germany	D-44791
41	Stadt. Kliniken	Dortmund		Germany	44123
42	Universitaet Erlangen	Erlangen		Germany	D-91054
43	Georg August Universitaet	Goettingen		Germany	D-37075
44	Haematologisch-Onkologische Praxis Altona	Hamburg		Germany	D-22765
45	Universitaets-Hautklinik Heidelberg	Heidelberg		Germany	D-69115
46	Universitaet Leipzig - Chirurgische Klinik und Poliklinik I	Leipzig		Germany	D-04103
47	Otto - Von - Guericke - Universitaet Magdeburg	Magdeburg		Germany	D-39120
48	Klinikum der Stadt Mannheim	Mannheim		Germany	D-68135
49	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg		Germany	D-97080
50	Rambam Medical Center	Haifa		Israel	31096
51	Wolfson Medical Center	Holon		Israel	58100
52	Tel-Aviv Sourasky Medical Center	Tel-Aviv		Israel	64239
53	Centro di Riferimento Oncologico - Aviano	Aviano		Italy	33081
54	Ospendale S.M. Annunziata-A.S.DI Firenze	Firenze		Italy	I-50011
55	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)		Italy	16132
56	Istituto Nazionale per lo Studio e la Cura dei Tumori	Milano (Milan)		Italy	20133
57	European Institute of Oncology - Chemo Prevention	Milano		Italy	20141
58	Istituto Nazionale per lo Studio e la Cura dei Tumori	Naples		Italy	80131
59	Istituto Regina Elena	Rome		Italy	00161
60	Universita Degli Studi di Torino	Torino		Italy	10126
61	Vrije Universiteit Medisch Centrum	Amsterdam		Netherlands	1007 MB
62	Leiden University Medical Center	Leiden		Netherlands	2300 CA
63	University Medical Center Nijmegen	Nijmegen		Netherlands	NL-6500 HB
64	Erasmus University Medical Center	Rotterdam		Netherlands	3075 EA
65	Academisch Ziekenhuis Utrecht	Utrecht		Netherlands	3584 CX
66	Great Poland Cancer Center	Poznan		Poland	61 866
67	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw		Poland	02-781
68	Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa	Lisbon		Portugal	1099-023 Codex
69	Instituto Portugues de Oncologia Centro do Porto, SA	Porto		Portugal	4200
70	Institute of Oncology, Ljubljana	Ljubljana		Slovenia	Sl-1000
71	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
72	Hospital Clinico Universitario	Zaragoza		Spain	50009
73	Kantonspital Aarau	Aarau		Switzerland	5001
74	Inselspital, Bern	Bern		Switzerland	CH-3010
75	Ratisches Kantons und Regionalspital	Chur		Switzerland	CH-7000
76	UniversitaetsSpital	Zurich		Switzerland	CH-8091
77	Vakif Gureba Training Hospital	Istanbul		Turkey	34296
78	Ege University Medical School	Izmir		Turkey	35220
79	Bristol Haematology and Oncology Centre	Bristol	England	United Kingdom	BS2 8ED
80	Addenbrooke's NHS Trust	Cambridge	England	United Kingdom	CB2 2QQ
81	Cheltenham General Hospital	Cheltenham	England	United Kingdom	GL53 7AN
82	Royal Devon and Exeter Hospital	Exeter	England	United Kingdom	EX2 5DW
83	Royal Surrey County Hospital	Guildford	England	United Kingdom	GU2 5XX
84	Princess Royal Hospital	Hull	England	United Kingdom	HU8 9HE
85	St. James's Hospital	Leeds	England	United Kingdom	LS9 7TF
86	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
87	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
88	Royal Free Hospital	London	England	United Kingdom	NW3 2QG
89	Guy's and St. Thomas' Hospitals NHS Trust	London	England	United Kingdom	SE1 9RT
90	St. George's Hospital	London	England	United Kingdom	SW17 0QT
91	Royal Marsden NHS Trust	London	England	United Kingdom	SW3 6JJ
92	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England	United Kingdom	CH63 4JY
93	Newcastle General Hospital	Newcastle Upon Tyne	England	United Kingdom	NE4 6BE
94	Salisbury District Hospital	Salisbury	England	United Kingdom	SP2 8BJ
95	Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
96	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
97	Royal Marsden Hospital	Sutton	England	United Kingdom	SM2 5PT
98	Southend NHS Trust Hospital	Westcliff-On-Sea	England	United Kingdom	SS0 0RY
99	Belfast City Hospital Trust	Belfast	Northern Ireland	United Kingdom	BT9 7AB
100	Ninewells Hospital and Medical School	Dundee	Scotland	United Kingdom	DD1 9SY
101	Western Infirmary	Glasgow	Scotland	United Kingdom	G11 6NT
102	Velindre Cancer Center at Velinde Hospital	Cardiff	Wales	United Kingdom	CF4 7XL
103	Selly Oak Hospital at University Hospital NHS Trust	Birmingham		United Kingdom	B29 6JD
104	Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC

Investigators

• Study Chair: Alexander M. M. Eggermont, MD, PhD, Daniel Den Hoed Cancer Center at Erasmus Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• ClinicalTrials.gov Identifier: NCT00006249
• Other Study ID Numbers: EORTC-18991; EORTC-18991
• First Posted: Jan 27, 2003
• Last Update Posted: Feb 10, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC: stage III melanoma
• Additional relevant MeSH terms: Melanoma; Interferons; Interferon-alpha

Study Results

No Results Posted as of Feb 10, 2015