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Melanoma Margins Excision Trial: A Randomised Controlled Trial Comparing 1cm Versus 2cm Excision Margins for Primary Cutaneous Melanoma

Phase 3
18 Years
85 Years
Not Enrolling

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Trial Information

Melanoma Margins Excision Trial: A Randomised Controlled Trial Comparing 1cm Versus 2cm Excision Margins for Primary Cutaneous Melanoma

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

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%.

Inclusion Criteria:

- • Patients must have a primary invasive cutaneous melanoma of Breslow thickness
greater than 1 millimetre as determined by diagnostic biopsy (narrow excision,
incision or punch biopsy) and subsequent histopathological analysis.

- Have a primary melanoma that is cutaneous (including head, neck, trunk,
extremity, scalp, palm, sole).

- Randomisation must take place within 90 days of original diagnosis

- Patients must be 18 years or over at time of consent.

- Patient must be able to give informed consent.

- Life expectancy of at least 10 years from the time of diagnosis, not considering
the melanoma in question, as determined by the PI.

- A survivor of prior cancer is eligible provided that ALL of the following
criteria are met and documented:

- The patient has undergone potentially curative therapy for all prior

- There has been no evidence of recurrence of any prior malignancies for at
least FIVE years (except for successfully treated cervical or non-melanoma
skin cancer with no evidence of recurrence), and

- The patient is deemed by their treating physician to be at low risk of
recurrence from previous malignancies

- The patient agrees to be followed up at an investigating centre for 10 years.

Exclusion Criteria:

- • Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown
malignant potential'.

- Patient has already undergone wide local excision at the site of the primary
index lesion.

- Patient has already undergone a local flap reconstruction of the defect after
excision of the primary and determination of an accurate excision margin is

- History of previous or concurrent (i.e., second primary) invasive melanoma.

- Melanoma located distal to the metacarpophalangeal joint, on the tip of the
nose, the eyelids or on the ear.

- Primary melanoma of the eye, ears, mucous membranes or internal viscera.

- Physical, clinical, radiographic or pathologic evidence of satellite,
in-transit, regional, or distant metastatic disease.

- Patient has undergone surgery on a separate occasion to clear the lymph nodes of
the probable draining lymphatic field, including sentinel lymph node biopsy, of
the index melanoma.

- Any additional solid tumor or hematologic malignancy during the past 5 years
except T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or
uterine cervical cancer.

- Skin grafts, tissue transfers or flaps that have the potential to alter the
lymphatic drainage

- Organic brain syndrome or significant impairment of basal cognitive function or
any psychiatric disorder that might preclude participation in the full protocol,
or be exacerbated by therapy (e.g., severe depression).

- Melanoma-related operative procedures not corresponding to criteria described in
the protocol.

- Primary or secondary immune deficiencies or known significant autoimmune

- History of organ transplantation.

- Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at
any time during study participation or within 6 months prior to enrolment.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Local Recurrence

Outcome Description:

Recurrence of melanoma in the scar or in the regional skin (in transits or satellites)

Outcome Time Frame:

10 years

Safety Issue:


Principal Investigator

Marc D Moncrieff, MD FRCS(plast.)

Investigator Role:

Principal Investigator

Investigator Affiliation:

Norfolk & Norwich University Hospital NHS Foundation Trust


United Kingdom: National Health Service

Study ID:




Start Date:

November 2012

Completion Date:

Related Keywords:

  • Melanoma
  • Melanoma
  • Cutaneous Melanoma
  • Skin Cancer
  • Surgery
  • Melanoma