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

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.

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