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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00006249




Registration number
NCT00006249
Ethics application status
Date submitted
11/09/2000
Date registered
27/01/2003
Date last updated
10/02/2015

Titles & IDs
Public title
Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma
Scientific title
PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial
Secondary ID [1] 0 0
EORTC-18991
Secondary ID [2] 0 0
EORTC-18991
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma (Skin) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
No intervention: observation - 5 years observation + 5 years follow up

Experimental: pegylated interferon alfa - 5 years pegylated interferon alfa + 5 years follow up
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
distant-metastasis free-survival (DMFS)
Timepoint [1] 0 0
from randomization
Secondary outcome [1] 0 0
survival
Timepoint [1] 0 0
from randomization till death
Secondary outcome [2] 0 0
toxicity
Timepoint [2] 0 0
from randomization

Eligibility
Key inclusion 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

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
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2000
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
1258
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [2] 0 0
Austin and Repatriation Medical Centre - Heidelberg West
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital, Perth - Perth
Recruitment hospital [5] 0 0
David Maddison Clincial Sciences - Newcastle
Recruitment postcode(s) [1] 0 0
8006 - East Melbourne
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment postcode(s) [5] 0 0
NSW 2300 - Newcastle
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Edegem
Country [3] 0 0
Belgium
State/province [3] 0 0
Gosselies
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Sofia
Country [6] 0 0
Croatia
State/province [6] 0 0
Zagreb
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Prague (Praha)
Country [8] 0 0
Estonia
State/province [8] 0 0
Tallinn
Country [9] 0 0
France
State/province [9] 0 0
Amiens
Country [10] 0 0
France
State/province [10] 0 0
Besancon
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Boulogne Billancourt
Country [13] 0 0
France
State/province [13] 0 0
Grenoble
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Limoges
Country [16] 0 0
France
State/province [16] 0 0
Lyon
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Nice
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Pessac
Country [21] 0 0
France
State/province [21] 0 0
Reims
Country [22] 0 0
France
State/province [22] 0 0
Rennes
Country [23] 0 0
France
State/province [23] 0 0
Saint Cloud
Country [24] 0 0
France
State/province [24] 0 0
Saint Priest en Jarez
Country [25] 0 0
France
State/province [25] 0 0
Strasbourg
Country [26] 0 0
France
State/province [26] 0 0
Thionville
Country [27] 0 0
France
State/province [27] 0 0
Tours
Country [28] 0 0
France
State/province [28] 0 0
Vandoeuvre-les-Nancy
Country [29] 0 0
France
State/province [29] 0 0
Villejuif
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Bochum 1
Country [32] 0 0
Germany
State/province [32] 0 0
Dortmund
Country [33] 0 0
Germany
State/province [33] 0 0
Erlangen
Country [34] 0 0
Germany
State/province [34] 0 0
Goettingen
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Germany
State/province [36] 0 0
Heidelberg
Country [37] 0 0
Germany
State/province [37] 0 0
Leipzig
Country [38] 0 0
Germany
State/province [38] 0 0
Magdeburg
Country [39] 0 0
Germany
State/province [39] 0 0
Mannheim
Country [40] 0 0
Germany
State/province [40] 0 0
Wuerzburg
Country [41] 0 0
Israel
State/province [41] 0 0
Haifa
Country [42] 0 0
Israel
State/province [42] 0 0
Holon
Country [43] 0 0
Israel
State/province [43] 0 0
Tel-Aviv
Country [44] 0 0
Italy
State/province [44] 0 0
Aviano
Country [45] 0 0
Italy
State/province [45] 0 0
Firenze
Country [46] 0 0
Italy
State/province [46] 0 0
Genoa (Genova)
Country [47] 0 0
Italy
State/province [47] 0 0
Milano (Milan)
Country [48] 0 0
Italy
State/province [48] 0 0
Milano
Country [49] 0 0
Italy
State/province [49] 0 0
Naples
Country [50] 0 0
Italy
State/province [50] 0 0
Rome
Country [51] 0 0
Italy
State/province [51] 0 0
Torino
Country [52] 0 0
Netherlands
State/province [52] 0 0
Amsterdam
Country [53] 0 0
Netherlands
State/province [53] 0 0
Leiden
Country [54] 0 0
Netherlands
State/province [54] 0 0
Nijmegen
Country [55] 0 0
Netherlands
State/province [55] 0 0
Rotterdam
Country [56] 0 0
Netherlands
State/province [56] 0 0
Utrecht
Country [57] 0 0
Poland
State/province [57] 0 0
Poznan
Country [58] 0 0
Poland
State/province [58] 0 0
Warsaw
Country [59] 0 0
Portugal
State/province [59] 0 0
Lisbon
Country [60] 0 0
Portugal
State/province [60] 0 0
Porto
Country [61] 0 0
Slovenia
State/province [61] 0 0
Ljubljana
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid
Country [63] 0 0
Spain
State/province [63] 0 0
Zaragoza
Country [64] 0 0
Switzerland
State/province [64] 0 0
Aarau
Country [65] 0 0
Switzerland
State/province [65] 0 0
Bern
Country [66] 0 0
Switzerland
State/province [66] 0 0
Chur
Country [67] 0 0
Switzerland
State/province [67] 0 0
Zurich
Country [68] 0 0
Turkey
State/province [68] 0 0
Istanbul
Country [69] 0 0
Turkey
State/province [69] 0 0
Izmir
Country [70] 0 0
United Kingdom
State/province [70] 0 0
England
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Northern Ireland
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Scotland
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Wales
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Birmingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00006249
Trial related presentations / publications
Eggermont AM, Suciu S, Testori A, Kruit WH, Marsden J, Punt CJ, Santinami M, Sales 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.
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 15): A-8506b, 2011.
Bouwhuis MG, Suciu S, Testori A, Kruit WH, Sales 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 autoantibodies--EORTC 18991. J Clin Oncol. 2010 May 10;28(14):2460-6. doi: 10.1200/JCO.2009.24.6264. Epub 2010 Apr 12.
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 (EORTC 18991). Cancer Chemother Pharmacol. 2010 Mar;65(4):671-7. doi: 10.1007/s00280-009-1072-z. Epub 2009 Jul 21.
Bottomley A, Coens C, Suciu S, Santinami M, Kruit W, Testori A, Marsden J, Punt C, Sales 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 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. 2009 Jun 20;27(18):2916-23. doi: 10.1200/JCO.2008.20.2069. Epub 2009 May 11. Erratum In: J Clin Oncol. 2009 Sep 20;27(27):4630. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.
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 adjuvant interferon treatment (EORTC 18991 side study). Eur J Cancer. 2009 Dec;45(18):3189-97. doi: 10.1016/j.ejca.2009.09.004. Epub 2009 Sep 28.
Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, Punt CJ, Sales 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 observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008 Jul 12;372(9633):117-126. doi: 10.1016/S0140-6736(08)61033-8.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Alexander M. M. Eggermont, MD, PhD
Address 0 0
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00006249