Excision Margins for Melanoma

(MelMarT Trial)

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Melanoma and Skin Cancer Trials Limited

Must not be taking: Immunosuppressive agents

Disqualifiers: Desmoplastic melanoma, Neurotropic melanoma, Microsatellitosis, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether removing a smaller margin of skin around a melanoma is as effective as removing a larger margin. Specifically, it compares a 1 cm margin to a 2 cm margin to determine if both approaches are equally safe in preventing cancer recurrence. The goal is to assess if a smaller removal area can enhance patients' quality of life without increasing the risk of recurrence. Suitable candidates for this trial have had a melanoma at least 1 mm thick removed and have not yet undergone the larger surgery. As an unphased trial, this study allows patients to contribute to research that could improve surgical methods and quality of life for melanoma patients.

Will I have to stop taking my current medications?

The trial requires that participants do not take oral or injected immunosuppressive medications during the study or within 6 months before joining. If you are on such medications, you may need to stop them to participate.

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

Research has shown that removing melanoma with a smaller margin, such as 1 cm, might be as safe as using a larger 2 cm margin. A detailed review of studies found that a 1 cm margin is as safe as a 2 cm margin for medium to thick melanomas, indicating that a smaller margin doesn't increase the chance of cancer returning. However, another study found a higher risk of melanoma recurrence in the nearby area with a 1 cm margin.

Overall, these findings suggest that a 1 cm margin is generally safe, but there is some risk of melanoma returning nearby. These points are important to consider when deciding to join this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial comparing excision margins for melanoma because it could refine surgical techniques, potentially improving patient outcomes. Currently, standard melanoma treatments typically involve wide local excision with a 1cm or more extensive margin, often paired with a sentinel lymph node biopsy. This trial specifically investigates the differences between a 1cm margin and a 2cm margin. The goal is to determine which margin size is more effective at preventing recurrence while minimizing unnecessary tissue removal. Ultimately, the findings could lead to more personalized surgical strategies, balancing effectiveness with cosmetic and functional preservation.

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

This trial will compare two approaches to excision margins for melanoma. Research has shown that removing melanoma with a 1 cm margin might not suffice for thicker tumors, particularly those more than 2 mm deep on the body and limbs. Participants in Arm A of this trial will receive a 1 cm margin excision. Studies have found that using a wider margin, like 2 cm, does not improve survival rates but is generally considered safer for preventing cancer recurrence at the same site. Participants in Arm B will receive a 2 cm margin excision. However, some evidence suggests that smaller margins might be equally effective and could enhance patients' quality of life by preserving more healthy skin. These findings are important when deciding how much skin to remove in melanoma treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Marc Moncrieff

Principal Investigator

Norfolk & Norwich University Hospital

Prof Michael Henderson

Principal Investigator

Peter MacCallum Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with a life expectancy of at least 10 years and an ECOG score of 0-1, who have had a primary cutaneous melanoma thicker than 1mm completely excised. They must be able to follow the trial protocol and have no history of organ transplants, immunosuppressive treatments in the past six months, or other cancers within five years (with some exceptions).

Inclusion Criteria

Patient must be able to give informed consent and comply with the treatment protocol and follow-up plan

My main cancer treatment and tests were done within 4 months of diagnosis.

My life expectancy is over 10 years, not counting my melanoma.

Exclusion Criteria

My skin condition is possibly cancerous but not confirmed.

The presence of microsatellite instability as defined by the AJCC 2009 guidelines.

My melanoma is located on specific areas like fingertips, nose tip, eyelids, ears, or internal organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

Up to 30 days

1 visit (in-person)

Follow-up

Participants are monitored for local melanoma recurrence, adverse events, and quality of life assessments

120 months

Regular visits at Baseline, 3, 6, 12, 24, and 60 months

Long-term Follow-up

Participants are monitored for overall survival and recurrence-free survival

120 months

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The MelmarT trial is comparing two surgical approaches for melanoma: one group will have their cancer removed with a smaller margin (1cm) around where the tumor was, while another group will have it removed with a larger margin (2cm). The goal is to see if smaller margins are just as effective without affecting survival.

How Is the Trial Designed?

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

ARM A: Experimental Arm Wide Local Excision = 1cm Margin + Sentinel Lymph Node Biopsy +/- Reconstruction

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

ARM B:Control Arm Wide Local Excision = 2cm 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+

Norfolk and Norwich University Hospitals NHS Foundation Trust

Collaborator

Trials

57

Recruited

29,800+

Peter MacCallum Cancer Centre, Australia

Collaborator

Trials

102

Recruited

23,700+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4737890/

Wide versus narrow excision margins for high-risk, primary ... Our findings suggest that a 1 cm excision margin is inadequate for cutaneous melanoma with Breslow thickness greater than 2 mm on the trunk and limbs.

2. 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 ...

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

The end of wide local excision (WLE) margins for melanoma WLE with wider margins (up to 5 cm) has never improved overall survival. •. Considering the (adjuvant) systemic therapy advanced, WLE has become obsolete.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03860883

NCT03860883 | Melanoma Margins Trial-II: 1cm v 2cm ... There is evidence that less radical margins of excision may be just as safe. This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of the ...

5. staging.seer.cancer.gov staging.seer.cancer.gov/eod_public/input/3.2/melanoma_skin/clinical_margin_width/?breadcrumbs=(~view_schema~,~melanoma_skin~)

Clinical Margin Width | EOD Data SEER*RSA Clinical margin width describes the margins from a wide excision for a melanoma primary. The margin width is measured by the surgeon prior to the procedure.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12192206/

Comparison of 1-cm Versus 2-cm Excision Margins for ... This systematic review and meta-analysis suggests that a 1 cm margin is as safe as a 2 cm margin for intermediate to thick melanomas, reducing the need for ...

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

Excision Margins in High-Risk Malignant Melanoma A 1-cm margin of excision was associated with a significantly increased risk of locoregional recurrence. There were 168 locoregional recurrences (as first ...