PegIntron Versus IntronA in CMAJCC Stage II (EADO 2001/CMII Trial)
Condition: Melanoma; Neoplasm Metastasis
MeSH terms: Melanoma; Neoplasm Metastasis
Study type: Interventional
Phase: Phase 3

Summary: 
      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: 
      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.
    

Intervention name(s): PegIntron; intron A
Intervention type(s): Drug; Drug
Intervention description(s): 100 mcg SC/week for 36 months; 3mui TIWW SC for 18 months
Intervention MeSH terms: Peginterferon alfa-2b
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Melanoma; Neoplasm metastasis; Interferon alfa-2b; Adjuvants; Randomized clinical trial; Disease-free survival time; Safety; Drug toxicity; Quality of life