Surgical Excision Margins for Melanoma

(MelMarT-II Trial)

Recruiting at 200 trial locations

Overseen By Melanoma and Skin Cancer Trials Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Melanoma and Skin Cancer Trials Limited

Must not be taking: Immunosuppressive agents

Disqualifiers: Uncertain diagnosis, Perineural invasion, Desmoplastic melanoma, Microsatellitosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

2998 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if removing a smaller margin of skin around a melanoma can be as safe as removing a larger margin while enhancing quality of life. Patients will be randomly assigned to have either a 1 cm or a 2 cm margin removed around their melanoma through a procedure called Wide Local Excision (WLE). This trial targets individuals with stage II invasive melanomas on the skin who have not undergone prior extensive treatments on the affected area. As an unphased trial, it offers patients the chance to contribute to important research that could improve future treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking oral or injected immunosuppressive agents, you may not be eligible to participate.

What prior data suggests that these surgical excision margins are safe for melanoma patients?

Research has shown that removing melanoma with either a 1 cm or 2 cm margin is generally safe for patients. Studies have found that a 1 cm margin is as safe as a 2 cm margin for removing medium to thick melanomas, meaning the smaller margin does not lead to more side effects or complications.

Current guidelines recommend a 1 cm margin for early-stage melanomas, reflecting confidence in its safety. However, a small risk exists that this margin might not remove all melanoma cells, which could be serious in some cases.

The 2 cm margin has been used longer and is known to reduce the chance of cancer returning in the same area. Some evidence suggests that a margin larger than 1 cm might improve outcomes, but overall, both margins are considered safe choices for removal. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether the size of the surgical excision margin—either 1cm or 2cm—affects outcomes for melanoma patients. Currently, the standard approach involves removing a wide margin of skin around the melanoma to ensure all cancerous cells are excised. This trial could lead to a better understanding of how margin size impacts recovery, recurrence, and potential side effects. If a smaller margin proves just as effective, it might mean less tissue removal, which could result in quicker recovery and better cosmetic results for patients.

What evidence suggests that this trial's treatments could be effective for melanoma?

This trial will compare the effectiveness of two surgical excision margins for melanoma: a 1 cm margin and a 2 cm margin. Research has shown that removing a 1 cm area around a melanoma is usually as safe as removing a 2 cm area. A detailed review of studies found that both sizes have similar rates of cancer recurrence and patient survival for medium to thick melanomas. This suggests that using a smaller area might not increase the chance of cancer returning. Another study supported that removing a wide area, whether 1 cm or 2 cm, helps eliminate nearby cancer cells and can improve survival. Overall, using smaller areas might be just as effective and could enhance patients' quality of life. ^{1 5 6 7 8}

Who Is on the Research Team?

Michael Henderson

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Marc Moncrieff

Principal Investigator

Norfolk & Norwich University Hospital

Are You a Good Fit for This Trial?

Adults over 18 with stage II primary invasive cutaneous melanoma, as defined by specific criteria, who can undergo surgery within 120 days of diagnosis. They should have a life expectancy of at least five years and be able to consent and follow the trial protocol. Those with certain types of melanoma or past cancers (except some successfully treated ones) are excluded.

Inclusion Criteria

My skin cancer is at an early stage but deep or ulcerated.

I can carry out all my usual activities without help.

I had surgery for my condition within 4 months of being diagnosed.

Exclusion Criteria

I am scheduled for radiation therapy at the melanoma site after surgery.

I cannot have or am not eligible for a specific lymph node biopsy.

I had surgery to remove lymph nodes affected by melanoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Intervention

Participants undergo wide local excision with either a 1cm or 2cm margin, including sentinel lymph node biopsy and possible reconstruction

1 day

1 visit (in-person)

Post-Surgery Follow-up

Participants are monitored for serious adverse events and surgery-related adverse events

12 months

Multiple visits (in-person and virtual)

Long-term Follow-up

Participants are monitored for disease-free survival, local recurrence, distant disease-free survival, and overall survival

Up to 120 months

What Are the Treatments Tested in This Trial?

Interventions

• Wide Local Excision = 1cm Margin
• Wide Local Excision = 2cm Margin

Trial Overview This study compares two surgical techniques for removing skin cancer: one uses a wider (2cm) and the other a narrower (1cm) margin around the tumor. The goal is to see if smaller margins are just as effective while improving quality of life.

How Is the Trial Designed?

Group I: Arm A (Wide Local Excision = 1cm Margin) Experimental Treatment 1 Intervention

1cm Wide Local Excision margin + Sentinel Lymph Node Biopsy +/- Reconstruction

Group II: Arm B (Wide Local Excision = 2cm Margin) Active Control 1 Intervention

2 cm Wide Local Excision margin + Sentinel Lymph Node Biopsy +/- Reconstruction

Wide Local Excision = 1cm Margin is already approved in European Union, United States for the following indications:

Approved in European Union as Wide Local Excision for:

• Primary invasive cutaneous melanoma

Approved in United States as Wide Local Excision for:

• Primary invasive cutaneous melanoma

Who Is Running the Clinical Trial?

Melanoma and Skin Cancer Trials Limited

Lead Sponsor

Trials

18

Recruited

6,500+

Zuyderland Medical Centre

Collaborator

Trials

26

Recruited

107,000+

Norfolk and Norwich University Hospitals NHS Foundation Trust

Collaborator

Trials

57

Recruited

29,800+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Cancer Trials Ireland

Collaborator

Trials

85

Recruited

25,600+

Published Research Related to This Trial

In a study of 79 patients with head and neck melanomas, reducing the margins of wide local excision (WLE) did not increase the local recurrence rate, with an overall recurrence rate of only 8.9% over an average follow-up of 71.3 months.

The findings suggest that it is safe to reduce surgical margins in H&N melanoma to preserve critical anatomical structures without compromising the effectiveness of the treatment, as local recurrence-free survival was similar between standard and reduced margin groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing margins of wide local excision in head and neck melanoma for function and cosmesis: 5-year local recurrence-free survival. Rawlani, R., Rawlani, V., Qureshi, HA., et al.[2015]

In a randomized controlled trial involving 936 patients with cutaneous melanoma thicker than 2 mm, a 2-cm surgical resection margin was found to be as effective as a 4-cm margin in terms of overall survival, with a 5-year survival rate of 65% in both groups.

The study indicates that a 2-cm resection margin is sufficient and safe for these patients, suggesting that wider margins may not provide additional survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Gillgren, P., Drzewiecki, KT., Niin, M., et al.[2015]

Only 6% of patients had positive histological margins after wide local excision (WLE) of cutaneous melanoma, but those with positive margins were typically older, had thicker tumors, and often had tumors located in the head and neck region.

Patients with positive margins at WLE had a significantly higher local recurrence rate (16.0%) compared to those with negative margins (6.9%), indicating the importance of achieving clear margins, especially in patients with identified risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors Predicting Positive Margins at Primary Wide Local Excision of Cutaneous Melanoma. Mangold, AR., Skinner, R., Dueck, AC., et al.[2017]

Routine wide local excision (WLE) for stage I/II cutaneous melanoma shows no significant benefit in overall survival compared to omitting the procedure, based on a review of six large trials.

WLE is associated with considerable postoperative morbidity, and evidence suggests that a complete diagnostic excision may be sufficient, warranting further research to potentially change current surgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The end of wide local excision (WLE) margins for melanoma ? Zijlker, LP., Eggermont, AMM., van Akkooi, ACJ.[2023]

In a study of 451 patients over 20 years, immediate reconstruction after wide local excision of head and neck cutaneous malignant melanoma did not show a higher recurrence rate compared to delayed reconstruction, indicating that immediate reconstruction is a safe option.

Factors such as ulceration and positive sentinel lymph nodes were found to increase the risk of melanoma recurrence, highlighting the importance of these prognostic indicators in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence Rates Over 20 Years in the Treatment of Malignant Melanoma: Immediate Versus Delayed Reconstruction. Koolen, PGL., Matos, TR., Ibrahim, AMS., et al.[2020]

In a study of 252 melanoma specimens, it was found that formalin-fixed specimens consistently shrank by about 14%, suggesting a need for a 15% correction factor when evaluating surgical margins after fixation.

The measured surgical margins taken during excision were not reliable predictors of the histologic margins, indicating that surgeons may need to reconsider how they assess and plan for excision margins in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation Between Surgical and Histologic Margins in Melanoma Wide Excision Specimens. Friedman, EB., Dodds, TJ., Lo, S., et al.[2019]

In a study of 26,440 patients with invasive melanoma, it was found that tumors located on the trunk were more likely to be treated with wider excisional margins than recommended, while those treated in academic settings were less likely to do so.

Importantly, using wider excisional margins did not lead to improved survival rates, supporting the existing guidelines that recommend specific margin sizes for melanoma surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wide Excisional Surgery in Invasive Melanoma Treatment: Factors Driving Non-compliance With National Guidelines. Huayllani, MT., Bagaria, SP., Restrepo, DJ., et al.[2020]

In a study of 807 wide local excisions (WLE) of melanomas initially diagnosed with complete excisional biopsy, residual melanoma was found in 34 cases (4.2%), indicating that residual disease can occur even after what is thought to be complete removal.

The lentigo maligna subtype of melanoma was identified as having a higher risk of residual disease in WLE specimens, suggesting that while WLE is effective for controlling primary tumors, it may not fully prevent local metastatic recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy. Bolshinsky, V., Lin, MJ., Serpell, J., et al.[2015]

A 1 cm excision margin for melanoma, regardless of tumor thickness, has been shown to be effective, with studies indicating no significant difference in locoregional recurrence or mortality rates compared to wider margins of 3 to 5 cm.

The procedure should be conducted in a surgical setting under light general anesthesia, emphasizing the importance of meticulous technique for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommended width of excision for primary malignant melanoma. O'Rourke, MG., Bourke, C.[2019]

In a study of 1345 melanoma cases treated with wide local excision (WLE), 4.2% had positive or equivocal margins, with risk factors including noncompliance with surgical margins and specific anatomic locations like the head and neck.

Key risk factors for positive margins included noncompliance with recommended margins (5.57 times more likely), location on sensitive areas (5.07 times more likely), and increasing age, highlighting the importance of adhering to surgical guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for positive or equivocal margins after wide local excision of 1345 cutaneous melanomas. Miller, CJ., Shin, TM., Sobanko, JF., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10930506/

A Review of Contemporary Guidelines and Evidence for Wide ... This paper reviews the evidence for current guidelines for wide local excision margins; explores the challenges of extrapolating the findings of previous ...

2. ejcancer.com ejcancer.com/article/S0959-8049(22)01331-4/fulltext

The end of wide local excision (WLE) margins for melanoma WLE aims to eradicate potential microsatellites around melanomas and thereby reduce local recurrence rates and improve overall survival.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925001479

does wide local excision after a complete diagnostic ... This study examines whether wide local excision (WLE) after complete diagnostic excision improves recurrence-free survival (RFS) in clinical stage I/II primary ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa030681

Excision Margins in High-Risk Malignant Melanoma Our findings suggest that, in a small number of patients, the melanoma cells that remain after excision with a 1-cm margin will prove fatal. We therefore ...

5. staging.seer.cancer.gov staging.seer.cancer.gov/eod_public/input/3.3/melanoma_skin/clinical_margin_width/?breadcrumbs=(~schema_list~),(~view_schema~,~melanoma_skin~)

Clinical Margin Width | EOD Data SEER*RSA The clinical margin width for wide local excision of a melanoma in situ should be at least 5 mm. Additional Info. Current version of the Commission on Cancer's ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922013314

The end of wide local excision (WLE) margins for melanoma WLE aims to eradicate potential microsatellites around melanomas and thereby reduce local recurrence rates and improve overall survival.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524624/

The role of wide local excision of a primary lesion in ... Since the initially advocated 5 cm margins, excision margins have decreased, and current guidelines now recommend an excision margin of 1 cm for T1–T2 melanoma ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03860883

NCT03860883 | Melanoma Margins Trial-II: 1cm v 2cm ... Procedure : Wide Local Excision = 1cm Margin. A wide local excision involves removing an extra "safety margin" of skin surrounding the original melanoma site ...