Nordic Adjuvant IFN Melanoma Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Nordic Randomized Phase III Trial of Two Different Durations of Adjuvant Therapy With Intermediate-dose Interferon Alfa-2b in Patients With High-risk Melanoma

Conditions
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Melanoma, Adjuvant Therapy

Intervention / Treatment
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* Drug: Interferon-alpha2b - 1 year
* Drug: Interferon-alpha2b - 2 years


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm A<br>Observation only - no therapy | |
| Experimental: Arm B Interferon 1 year<br>Interferon Therapy: Induction: IFN-alfa2b, 10 MU (flat dose), SC, 5 days/week, 4 weeks Maintenance: IFN-alfa2b, 10 MU (flat dose), 3 days/week, SC, 12 months | Drug: Interferon-alpha2b - 1 year<br>* Induction: IFN-alpha2b, 10 MU (flat dose), SC, 5 days/week, 4 weeks Maintenance: IFN-alpha2b, 10 MU (flat dose), 3 days/week, SC, 12 months<br>* Other names: Intron-A;|
| Experimental: Arm C Interferon 2 years<br>Two year arm Induction: IFN-alfa2b, 10 MU (flat dose), SC, 5 days/week, 4 weeks Maintenance: IFN-alfa2b, 10 MU (flat dose), 3 days/week, SC, 24 months | Drug: Interferon-alpha2b - 2 years<br>* Induction: IFN-alfa2b, 10 MU (flat dose), SC, 5 days/week, 4 weeks Maintenance: IFN-alfa2b, 10 MU (flat dose), 3 days/week, SC, 24 months<br>* Other names: Intron-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | All registered deaths, not only melanoma-specific. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse free survival | Time from randomization to date of first reported melanoma recurrence or death | Evaluated at regular intervals | 
| Safety-toxicity | All toxicities and SAEs are recorded and classified according to CTC v2.0 criteria | Regular evaluations | 
| Health related quality of life | Recorded by using the EORTC QLQ-C30 questionnaire at nine time points during treatment and follow-up | Regular evaluations | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Phase III trial, Adjuvant therapy, Interferon, Melanoma