PegIntron Versus IntronA in CMAJCC Stage II (EADO 2001/CMII Trial)

Study Overview
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Brief Summary
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Melanoma with a tumor thickness >= 1.5mm without clinically detectable nodes represents an increasing population with relapse rate of more than 50%. Adjuvant therapy with low doses of IFN alpha can provide a benefit in this group. However, the impact of low dose IFN alpha is not sustained after the treatment period. A longer treatment may prolong the benefit and thus have a more clear-cut impact on disease-free and overall survival. The tolerance and the impact on quality of life are limiting factors in a group of patients whose individual course is not necessarily poor. PegIntron may be better tolerated than instant release interferon, and thus make this treatment more acceptable in terms of toxicity and quality of life. Thus treatment schedule with PegIntron is not expected to increase the cost of standard care significantly.

Detailed Description
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Study design and primary objective This is an European multicenter, open label, prospective randomized phase III trial evaluating the efficacy of long-term maintenance therapy of two therapy options, IntronA for 18 months versus PegIntron for 36 months, administered in an adjuvant setting after the local excision of an intermediate risk cutaneous melanoma. Eligibility criteria Intermediate risk melanoma is defined by the following criteria: (1) a tumor thickness >= 1,5mm and (2) the absence of regional nodal macrometastases, as assessed either by clinical examination or, if sentinel lymph node biopsy (SLNB) or elective node dissection (ELND) are performed, by the absence of macroscopic evidence of disease. Patients with evidence of nodal micrometastasis by SLNB or ELND are eligible. The choice of performing sentinel node dissection will be left to the decision of each center, on condition to concern all consecutive patients and that all surgical procedures are completed before randomization of the patients . The centers have to inform their respective national study center if they perform SLNB or ELND and also if they change their surgical procedure. Study treatments Arm A : PegIntron 100 mcg SC/week for 36 months Arm B : IntronA 3miu TIWW SC for 18 months Endpoints The primary endpoint of the study will be the time to any recurrence (local recurrence, satellite or in transit metastasis, regional node metastasis or distant metastasis) or death, whatever the cause. The primary comparison between the two arms will use the 5-year disease-free survival time. Secondary endpoints are time to distant metastasis , overall survival, toxicity and quality of life. Therapy with either PegIntron or IntronA will continue as scheduled unless there is evidence of disease progression (whether local or distant recurrence), severe toxicity, or the subject requests that therapy be discontinued. All patients will be followed for disease-free-survival and overall survival until the end of the trial. Sample size and analysis The calculated sample size is 1190 patients to be enrolled over a 5 years period; this sample size is inclusive of an expected lost to follow up not more than 10% during the course of the trial. The randomization procedure will be stratified according to centers and to sentinel node biopsy. The primary analysis will be performed under the intent to treat principle.

Official Title
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Randomized, Multicenter Phase III Trial Comparing Adjuvant Treatment With PegIntron Over 36 Months Versus Reference Treatment With IntronA Over 18 Months in Cutaneous Melanoma Patients AJCC Stage II (>=1.5 mm Clinically Node Negative)

Conditions
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Melanoma, Neoplasm Metastasis

Intervention / Treatment
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* Drug: PegIntron
* Drug: intron A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven cutaneous melanoma Tumour thickness >= 1.5 mm (Breslow staging) Absence of clinically detectable regional node metastasis, no evidence of distant metastasis Informed consent form signed Exclusion Criteria: Any prior chemo-, immuno-, hormonal or radiation therapy Macroscopic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: A<br>Peg Intron 100 mcg SC/week for 36 months | Drug: PegIntron<br>* 100 mcg SC/week for 36 months<br>|
| Active Comparator: B<br>Intron A 3 X 3 MIU, weekly, sc, for 18 months | Drug: intron A<br>* 3mui TIWW SC for 18 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival time |  | 5-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to distant metastasis |  | the time from the inclusion to the first documentation of any distant metastasis | 
| overall survival |  | the time from the inclusion to the date of death regardless of the specific cause | 
| toxicity |  | for 36 months | 
| quality of life |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Neoplasm metastasis, Interferon alfa-2b, Adjuvants, Randomized clinical trial, Disease-free survival time, Safety, Drug toxicity, Quality of life