Adjuvant PEG Intron in Ulcerated Melanoma

Phase 3

• Conditions: Ulcerated Melanomas
• Interventions: Biological: PEG IFN alfa-2b

• Registration Number: NCT01502696
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-22
• Study First Submitted QC: 2011-12-29
• Study First Posted: 2012-01-02
• Study Start: 2012-10
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-28
• Last Update Posted: 2019-03-04
• Primary Completion: 2019-04
• Study Completion: 2019-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PEG IFN alfa-2b	PEG IFN alfa-2b	-

Primary Outcome Measures

Name	Time	Method
Relapse-free survival (RFS)	6.3 years from first patient in

Secondary Outcome Measures

Name	Time	Method
Distant metastases-free survival (DMFS)	7.8 years from first patient in
Overall survival (OS)	7.8 years from first patient in
Quality of life	6 years from from first patient in
Occurence of Adverse Events	6.3 years from first patient in	This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

Trial Locations

Locations (57)

Hospital Distrital De Santarem; 🇵🇹 Santarem, Portugal

Universitaetsklinikum; 🇩🇪 Essen, Germany

Universitaetsklinikum Heidelberg - Hautklinik / Dermatologic Department; 🇩🇪 Heidelberg, Germany

Universitaetsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

I.P.O. Francisco Gentil - Centro De Lisboa; 🇵🇹 Lisboa, Portugal

Universitaetsklinikum Wuerzburg; 🇩🇪 Wuerzburg, Germany

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis; 🇳🇱 Amsterdam, Netherlands

Leiden University Medical Centre; 🇳🇱 Leiden, Netherlands

Mid Essex Hospitals - Broomfield Hospital; 🇬🇧 Broomfield, United Kingdom

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital; 🇬🇧 Glasgow, United Kingdom

Universitaetsklinikum Heidelberg - Hautklinik; 🇩🇪 Heidelburg, Germany

Universitaetsklinikum Koeln; 🇩🇪 Koeln, Germany

Medizinische Universitaet Zu Luebeck; 🇩🇪 Luebeck, Germany

Cheltenham General Hospital; 🇬🇧 Cheltenham, United Kingdom

Hospital Clinic Universitari; 🇪🇸 Barcelona, Spain

Clatterbridge Centre for Oncology NHS Trust - Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Bebington, United Kingdom

Vrije Universiteit Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"; 🇮🇹 Napoli, Italy

Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center; 🇩🇪 Mainz, Germany

Leeds Teaching Hospitals NHS Trust - St. James's University Hospital; 🇬🇧 Leeds, United Kingdom

Hospital Universitario 12 De Octubre; 🇪🇸 Madrid, Spain

University Hospitals Birmingham NHS Foundation Trust (UHB) - Queen Elisabeth Medical Centre; 🇬🇧 Birmingham, United Kingdom

St George's Hospital NHS Trust (6961); 🇬🇧 London, United Kingdom

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Norfolk And Norwich Hospital; 🇬🇧 Norwich, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital; 🇬🇧 Nottingham, United Kingdom

Medical University of Graz; 🇦🇹 Graz, Austria

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Universitair Ziekenhuis Gent; 🇧🇪 Ghent, Belgium

Herlev Hospital - University Copenhagen; 🇩🇰 Herlev, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre (Bordeaux, France; 🇫🇷 Bordeaux, France

Assistance Publique - Hopitaux de Paris - Hopital Avicenne; 🇫🇷 Bobigny, France

CHU de Grenoble - La Tronche - Hôpital A. Michallon; 🇫🇷 Grenoble, France

CHRU de Lille; 🇫🇷 Lille, France

Centre Leon Berard; 🇫🇷 Lyon, France

Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone; 🇫🇷 Marseille, France

CHU de Nice - CHU de Nice - Hopital De L'Archet; 🇫🇷 Nice, France

Assistance Publique - Hopitaux de Paris - CHU Ambroise Pare; 🇫🇷 Paris, France

Assitance Publique - Hopitaux de Paris - Hopital Bichat-Claude Bernard; 🇫🇷 Paris, France

Assitance Publique - Hopitaux de Paris - Hopital Saint-Louis; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Paris, France

Centre Hospitalier De Pau; 🇫🇷 Pau, France

CHU de Reims - Hôpital Robert Debré; 🇫🇷 Reims, France

CHU d'Amiens - CHU Amiens - Hopital Sud; 🇫🇷 Salouel, France

UniversitaetsMedizin Mannheim; 🇩🇪 Mannheim, Germany

IRCCS - Istituto Tumori "Giovanni Paolo II"; 🇮🇹 Bari, Italy

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" di Udine; 🇮🇹 Udine, Italy

Istituto Dermopatico Dell'Immacolata; 🇮🇹 Roma, Italy

Cambridge University Hospital NHS - Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

St Helens and Knowsley Teaching Hospitals; 🇬🇧 St Helens, United Kingdom

UniversitaetsSpital Zurich; 🇨🇭 Zurich, Switzerland

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet; 🇧🇪 Brussels, Belgium

U.Z. Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Maria Sklodowska-Curie Memorial Cancer Centre; 🇵🇱 Warsaw, Poland