Melanoma Margins Trial (MelMarT): A Phase III, Multi-Centre, Multi-National Randomised Control Trial Investigating 1cm v 2cm Wide Excision Margins for Primary Cutaneous Melanoma.

Inclusion Criteria

1. Patients must have a stage II primary invasive cutaneous melanoma with Breslow

thickness >2mm without ulceration), or >1mm (with ulceration only) (pT2b-pT4b, AJCC

8th edition) as determined by diagnostic biopsy (narrow excision, incision or punch

biopsy) and subsequent histopathological analysis.

2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,

extremity, scalp, palm or sole).

3. An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary

melanoma.

4. Surgery (which refers to the staging sentinel node biopsy and wide local excision as

these are both to be done on the same day) must be completed within 120 days of the

original diagnosis.

5. Patients must be 18 years or older at time of consent.

6. Patient must be able to give informed consent and comply with the treatment protocol

and follow-up plan.

7. Life expectancy of at least 5 years from the time of diagnosis, not considering the

melanoma in question, as determined by the PI.

8. Patients must have an ECOG performance score between 0 and 1.

9. 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

malignancies,

- 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.

Exclusion Criteria

Patients will be excluded from the study for ANY of the following reasons:

1. Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown

malignant potential'.

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

lesion.

3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the

primary index lesion.

4. Desmoplastic or neurotropic melanoma: with any patient where pathology determines

melanoma as PURE desmoplastic (as per WHO definition of >90% desmoplasia), they are

not eligible for this study. However other desmoplasia or mixed subtypes are eligible

unless there is neurotropism present (peri-neural invasion).Peri-neural invasion does

not include entrapment of nerves within the main primary tumour mass.

Microsatellitosis as per AJCC 8th edition definition

5. Subungual melanoma

6. Patient has already undergone a local flap reconstruction of the defect after excision

of the primary and determination of an accurate excision margin is impossible.

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

8. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the

eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal

viscera.

9. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,

regional, or distant metastatic melanoma.

10. 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.

11. Any additional solid tumour or hematologic malignancy during the past 5 years except

T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical

cancer.

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

protocol.

13. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision

is not permitted as part of the protocol and any patients given this treatment would

be excluded from the study.

14. History of organ transplantation.

15. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at

enrolment or within 6 months prior to enrolment.

Pregnancy is not a specific exclusion criterion for this trial, though it may not be

clinically appropriate to perform a wide excision and sentinel node biopsy until the

pregnancy has been completed, which is likely to exclude the patient due to violation of

inclusion criterion 4. We would advise careful counselling of the patient prior to

enrolling the patient, which would include a discussion at the treating centre's

multidisciplinary team meeting or tumour board. We would strongly advise contacting the

central trial office to discuss the case prior to enrolling on the study.