Melanoma Margins Excision Trial (MelMarT)

• Local Recurrence [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Recurrence of melanoma in the scar or in the regional skin (in transits or satellites)
  
  
• Melanoma Specific Survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Death from melanoma druing the study period
  
  

• Quality of Life [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Qulaity of Life after surgery
  
  
• Health Economical Analysis [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  A measure of health care expenses between the two groups and clinical effectiveness
  
  
• Surgical Complication Rate [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  The incidence of morbidity and moratlity associated with the surgery
  
  

Aim To conduct a RCT to establish whether there is a difference between local recurrence (wound scar, in-transit or satellite recurrence) for patients treated with a 1cm vs 2cm radial excision margin for >1mm thick primary invasive melanomas.

To determine, with the evidence provided by a RCT, the safety and efficacy of treatment of >1mm Breslow thickness primary invasive melanoma using a 1cm vs 2cm radial excision margin. Measurable endpoints are local recurrence; melanoma-specific and disease-free survival. Secondary endpoints will include patient satisfaction with their surgical treatment and scars as part of a quality of life assessment using structured questionnaires, in addition to an analysis on length of hospital stay and surgical complication rate which will provide an indirect assessment of financial and health care burden the two treatment arms entail.

Study design The study design follows a large simple trial format of a phase III randomised clinical non-inferiority study comparing 1cm excision margins (ARM A) versus 2cm excision margin (ARM B) for cutaneous melanomas >1mm in Breslow thickness. The non-inferiority study will provide the opportunity to rule out small but clinically important lower local recurrence rate in the 1cm margin arm. Local recurrence rate is the primary endpoint. For the purpose of this study, local recurrence rate will be include recurrence adjacent to the scar, satellite lesions and in transit metastases distal to the primary draining nodal field.

The accrual goal is 10,000 patients over 7 years with an equal number of patients in each arm The final assessment of overall local recurrence rate will be at ten years following completion of patient accrual. Some secondary endpoint analyses will also be performed at 1 and 5 years post-treatment Outcome measurements

Primary endpoint:

- Local recurrence rate

Secondary endpoints:

• Regional recurrence rate
• Melanoma-specific survival
• Surgical Complications
• Duration of hospital stay
• Quality of Life analysis
• Health Economics Analysis - Clinical Effectiveness Population Patients with a >1 mm Breslow thickness primary cutaneous melanoma, in a body area where a 2cm radial margin of resection is technically feasible, who are able to consent to the study Data Analysis A survival analysis will be used to analyse the primary endpoint (local recurrence) using Cox's Proportional Hazards model. Non-inferiority will be based upon the hazard ratio; if the upper 95% confidence limit does not exceed a ratio of 1.5 (1cm group to 2cm group) non-inferiority will be accepted. The study sample size is based upon a recurrence rate of 2% in ARM B (i.e. 2cm margin group). Thus, non-inferiority will imply a recurrence of less than 3% in ARM A (1cm margin) group. Each arm will require 4605 patients to provide a 90% statistical power to detect a difference of this magnitude. Allowing for loss to follow-up of 10%, 10,000 patients will be required.

Null Hypothesis As a non-inferiority study, the null hypothesis is that there is an increase in local recurrence rate in ARM A (1cm margin group) compared to ARM B of at least 1%.