Clinical trial NCT01259934: Nordic Adjuvant IFN Melanoma Trial
Official title: Nordic Randomized Phase III Trial of Two Different Durations of Adjuvant Therapy With Intermediate-dose Interferon Alfa-2b in Patients With High-risk Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Adjuvant Therapy
Keywords: Randomized Phase III trial
Adjuvant therapy
Interferon
Melanoma
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-12-14
Enrollment: 855
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of giving adjuvant treatment with intermediate doses of interferon-alpha2b to patients operated for high risk melanoma. Patients are randomly assigned to either observation only or interferon treatment for 2 different durations. The outcome with respect to overall survival, relapse-free survival, side effects and quality of life is analysed.

Detailed description: This is an open multicenter, prospective randomised phase III trial evaluating the efficacy of two different schedules of Interferon-alpha2b (IFN-alpha2b) administered in an adjuvant setting after adequate surgery in high risk cutaneous melanoma patients (T4N0M0/TxN1-2M0). The patients have been operated for either a thick primary melanoma (\> 4 mm) without evidence of distant metastasis or have undergone surgery for regional lymph node metastases.

The study consists of a control arm (A) and two treatment arms, B and C. The outcome in arms B and C with adjuvant treatment with IFN-alpha2b will be compared to the outcome of arm A in which the patients will only be observed after the surgery. The primary endpoint is overall survival. Secondary endpoints are relapse-free survival, safety-toxicity and health-related quality of life.

Eligibility criteria: Inclusion Criteria:

* T4 N0 M0 - Thick primary melanoma: \> 4.0 mm Breslow depth, without lymph node involvement, or
* Tx N1-2 M0 Primary melanoma of any thickness with regional lymph node metastases confirmed by lymphadenectomy, or
* Tx N1-2 M0 Recurrent melanoma in regional lymph node(s) confirmed by lymphadenectomy.
* ECOG performance status of 0-1
* No active medical or psychiatric disorder requiring therapy that would prevent completion of protocol
* Written informed consent

Exclusion Criteria:

* Patients with unknown primary site of melanoma or primary melanoma originating apart from the skin, except subungual melanoma
* Patients who have clinical, radiological/laboratory or pathological evidence of incompletely resected melanoma or distant metastatic disease
* Patients who have had prior adjuvant radiotherapy, chemotherapy, immunotherapy including preoperative infusion or perfusion therapy
* Female patients who are pregnant or lactating

Primary outcomes:
measure: Overall survival
timeFrame: Evaluated at regular intervals: every 3 months for 2 years, every 6 months up to 5 years and yearly up to 10 years following randomization. Actual median follow-up is 72.4 months
Secondary outcomes:
measure: Relapse free survival
timeFrame: Evaluated at regular intervals
measure: Safety-toxicity
timeFrame: Regular evaluations
measure: Health related quality of life
timeFrame: Regular evaluations
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet, Karolinska University Hospital,
Study officials:
affiliation: Karolinska Institutet
name: Johan Hansson, MD,PhD
role: STUDY_CHAIR
affiliation: Oslo University Hospital, Oslo, Norway
name: Steinar Aamdal, MD. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Lars Bastholt, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Helsinki, Finland
name: Micaela Hernberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahlgrenska University Hospital
name: Ulrika Stierner, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Copenhagen University Hospital, Copenhagen, Denmark
name: Hans von der Maase, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bouwhuis MG, Suciu S, Collette S, Aamdal S, Kruit WH, Bastholt L, Stierner U, Sales F, Patel P, Punt CJ, Hernberg M, Spatz A, ten Hagen TL, Hansson J, Eggermont AM; EORTC Melanoma Group and the Nordic Melanoma Group. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon. J Natl Cancer Inst. 2009 Jun 16;101(12):869-77. doi: 10.1093/jnci/djp132. Epub 2009 Jun 9.
citation: Prasmickaite L, Berge G, Bettum IJ, Aamdal S, Hansson J, Bastholt L, Oijordsbakken M, Boye K, Maelandsmo GM. Evaluation of serum osteopontin level and gene polymorphism as biomarkers: analyses from the Nordic Adjuvant Interferon alpha Melanoma trial. Cancer Immunol Immunother. 2015 Jun;64(6):769-76. doi: 10.1007/s00262-015-1686-4. Epub 2015 Apr 2.
citation: Hansson J, Aamdal S, Bastholt L, Brandberg Y, Hernberg M, Nilsson B, Stierner U, von der Maase H; Nordic Melanoma Cooperative Group. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial. Lancet Oncol. 2011 Feb;12(2):144-52. doi: 10.1016/S1470-2045(10)70288-6. Epub 2011 Jan 20.