Clinical trial NCT01502696: Adjuvant PEG Intron in Ulcerated Melanoma
Official title: Adjuvant Pegylated-Interferon-alpha2b (SylatronTM) for 2 Years Versus Observation in Patients With an Ulcerated Primary Cutaneous Melanoma With T(2-4)bN0M0: a Randomized Phase III Trial of the EORTC Melanoma Group.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ulcerated Melanomas
Keywords: ulcerated primary cutaneous melanoma
Stage II
PEG IFN alfa-2b
T(2-4)bN0M0
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: NCIC Clinical Trials Group
First posted: 2012-01-02
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with an ulcerated melanoma with Breslow \>1 mm, N0M0 have a significantly higher risk for relapse than patients with a non-ulcerated primary and about a 40-50% chance of developing stage IV disease to which they will almost invariably succumb. In stage I and II patients with an ulcerated primary who have been sentinel node (SN-staged) and found to be SN-negative there is still a 25-30% relapse risk.

The purpose of this study is to evaluate the effectiveness and safety when treated with PEG IFN alfa-2b for 2 years as compared to observation (no treatment), administered after adequate surgery has been performed for ulcerated primary cutaneous melanomas.


Eligibility criteria: Inclusion Criteria:

* Subjects must be between 18-70 years old.
* Subjects must have histologically documented ulcerated primary cutaneous melanomas with T(2-4)b N0M0.

Adequate resection of ulcerated primary cutaneous melanoma. 1 to 2 cm normal tissue excision margins according to Breslow thickness are recommended. In the head and neck areas and in case of locations distally on extremities, narrower margins are acceptable as long as they are radical (see Appendix F). Subjects must have recovered from the effects of recent surgery.

* SNB must occur within 12 weeks prior randomization.
* Subjects must have an ECOG performance status of 0 or 1 (See Appendix B).
* Subjects must have adequate bone marrow, renal and hepatic function as defined by the following parameters obtained up to maximum 12 weeks prior to randomization:

  * Hematology:
  * WBC \>= 3.0 x 109/L
  * Neutrophils \> 1.5 x 109/L
  * Platelets \> 100 x 109/L
  * Hemoglobin \>= 9 g/dL or 5.6 mmol/L
  * Adequate Renal and Hepatic function:
  * Serum creatinine \< 2.0 mg/dL or \< 140 µmol/L
  * SGOT and SGPT \< 2 times upper normal limit of laboratory normal (ULN)

Exclusion Criteria:

* No mucosal melanoma nor ocular melanoma.
* No evidence of nodal involvement confirmed by sentinel lymph node biopsy (SNB). Sentinel Node staging after the excision of the primary must be done between the date of final excision of the primary and the date of randomization.
* No evidence of regional nor distant lymph node metastases nor satellites/in-transit metastases (even if they have been resected).
* No evidence of distant metastasis on clinical examination, CT/MRI of full chest, abdomen and pelvis. Neck CT/MRI if head and neck primary.
* No clinical evidence of brain metastasis.
* No pregnant women
* No breast feeding women
* No patients with a medical condition requiring chronic systemic corticosteroids are not eligible.
* No experimental therapy within 30 days prior to randomization in this study.
* No prior chemotherapy, immunotherapy/vaccine, hormonal or radiation therapy for melanoma.
* No prior treatment with interferon-alfa for any reason.
* No history of prior malignancy within the past 5 years other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ.
* No severe cardiovascular disease, i.e. arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) nor symptomatic ischemic heart disease.
* No thyroid dysfunction not responsive to therapy.
* No poorly controlled (HBA1C\>8%) diabetes mellitus or uncontrolled diabetes mellitus, i.e. elevated fasting serum glucose should be \< 110% ULN).
* No active autoimmune disease.
* No active and/or uncontrolled infection, including active hepatitis.
* No history of seropositivity for HIV.
* No history of neuropsychiatric disorder requiring hospitalization.
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Primary outcomes:
measure: Relapse-free survival (RFS)
timeFrame: 6.3 years from first patient in
Secondary outcomes:
measure: Occurence of Adverse Events
timeFrame: 6.3 years from first patient in
measure: Overall survival (OS)
timeFrame: 7.8 years from first patient in
measure: Distant metastases-free survival (DMFS)
timeFrame: 7.8 years from first patient in
measure: Quality of life
timeFrame: 6 years from from first patient in
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Brussels
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital - University Copenhagen
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bobigny
country: France
facility: Assistance Publique - Hopitaux de Paris - Hopital Avicenne
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre (Bordeaux, France
city: Grenoble
country: France
facility: CHU de Grenoble - La Tronche - Hôpital A. Michallon
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone
city: Nice
country: France
facility: CHU de Nice - CHU de Nice - Hopital De L'Archet
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris - CHU Ambroise Pare
city: Paris
country: France
facility: Assitance Publique - Hopitaux de Paris - Hopital Bichat-Claude Bernard
city: Paris
country: France
facility: Assitance Publique - Hopitaux de Paris - Hopital Saint-Louis
city: Paris
country: France
facility: Institut Gustave Roussy
city: Pau
country: France
facility: Centre Hospitalier De Pau
city: Reims
country: France
facility: CHU de Reims - Hôpital Robert Debré
city: Salouel
country: France
facility: CHU d'Amiens - CHU Amiens - Hopital Sud
city: Essen
country: Germany
facility: Universitaetsklinikum
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg - Hautklinik / Dermatologic Department
city: Heidelburg
country: Germany
facility: Universitaetsklinikum Heidelberg - Hautklinik
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Luebeck
country: Germany
facility: Medizinische Universitaet Zu Luebeck
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
city: Mannheim
country: Germany
facility: UniversitaetsMedizin Mannheim
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Bari
country: Italy
facility: IRCCS - Istituto Tumori "Giovanni Paolo II"
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
city: Roma
country: Italy
facility: Istituto Dermopatico Dell'Immacolata
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" di Udine
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Centre
city: Lisboa
country: Portugal
facility: I.P.O. Francisco Gentil - Centro De Lisboa
city: Lisboa
country: Portugal
facility: I.P.O. Francisco Gentil - Centro De Lisboa
city: Santarem
country: Portugal
facility: Hospital Distrital De Santarem
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zurich
city: Bebington
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust - Clatterbridge Cancer Centre NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust (UHB) - Queen Elisabeth Medical Centre
city: Broomfield
country: United Kingdom
facility: Mid Essex Hospitals - Broomfield Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital NHS - Addenbrookes Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust - St. James's University Hospital
city: London
country: United Kingdom
facility: St George's Hospital NHS Trust (6961)
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk And Norwich Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
city: St Helens
country: United Kingdom
facility: St Helens and Knowsley Teaching Hospitals
Study officials:
affiliation: Institut Gustave Roussy, Paris, France
name: Alexander Eggermont, MD, PHD
role: STUDY_CHAIR
References: