Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma

Cutaneous Melanoma, Stage II Clinical Trial

— MelMarT-II  

Official title:

Melanoma Margins Trial-II - A Phase III, Multi-centre Randomised Controlled Trial Investigating 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (02.18 MelMarT-II)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03860883
• Other study ID #: 02.18
• Status: Recruiting
• Phase: Phase 3
• Start date: December 17, 2019
• Est. completion date: December 31, 2034

Study information

• Verified date: July 2023
• Source: Melanoma and Skin Cancer Trials Limited
• Contact: Melanoma and Skin Cancer Trials Coordinator
• Phone: +61 3 9903 9022
• Email: melmart[@]masc.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with a primary invasive melanoma are recommended to undergo excision of the primary lesion with a wide margin. 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 primary lesion for adult patients with stage II primary invasive cutaneous melanomas (AJCC 8th edition) to determine differences in disease-free survival. A reduction in margins is expected to improve patient quality of life.

Description:

This study will determine whether there is a difference in disease-free survival rates for patients with primary cutaneous melanoma with Breslow thickness > 2mm or 1-2mm with ulceration (pT2b-pT4b, AJCC 8th edition), treated with either a 1cm excision margin or 2cm margin. The study is designed to be able to prove or disprove that there is no difference in risk of the tumour recurring around the scar or anywhere else in the body between the two groups of patients. If the study shows no risk of tumour recurrence then we will also be able to determine how much of an impact the narrower excision has on patients in terms of improved quality of life and reduced side effects from the surgery and melanoma disease. This trial will also evaluate and determine the economic impact of narrower excision margins on the health services and society in general.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2998
• Est. completion date: December 31, 2034
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cutaneous Melanoma, Stage II
• Melanoma
• Skin Neoplasms

Intervention

Procedure:
• Wide Local Excision = 1cm Margin
A wide local excision involves removing an extra "safety margin" of skin surrounding the original melanoma site, to ensure that any remaining scattered melanoma tumour cells that may have been left behind after the first initial biopsy/surgery are removed.
• Wide Local Excision = 2cm Margin
A wide local excision involves removing an extra "safety margin" of skin surrounding the original melanoma site, to ensure that any remaining scattered melanoma tumour cells that may have been left behind after the first initial biopsy/surgery are removed.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Calvary Public Hospital Bruce	Bruce	Australian Capital Territory
Australia	The Canberra Hospital	Garran	Australian Capital Territory
Australia	Robina Hospital	Gold Coast	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Melanoma Institute Australia	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Hotel-Dieu de Quebec	Québec City	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	UHN - Princess Margaret Cancer Centre	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Italy	IOV Istituto Oncologico Veneto IRCCS-Padova	Padova
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	AOU Città della Salute e della Scienza di Torino	Torino
Netherlands	Flevo Hospital	Almere	Flevoland
Netherlands	Ziekenhuis Gelderse Vallei	Ede	Gelderland
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Zuyderland Medical Center	Heerlen
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Gelre Hospital	Zutphen	Gelderland
New Zealand	North Shore Hospital	Auckland
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Central Hospital Kristianstad	Kristianstad
United Kingdom	North Bristol NHS Trust	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Queen Victoria Hospital NHS Foundation Trust	East Grinstead	West Sussex
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Edgbaston	Birmingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Headington	Oxford
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull	East Yorkshire
United Kingdom	The Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	St. Helens & Knowsley Teaching Hospitals NHS Trust	Liverpool
United Kingdom	Guy's and St Thomas's NHS Foundation Trust, of St Thomas' Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust	London	The Bays
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	St George's University Hospitals NHS Foundation Trust	London
United Kingdom	The Royal Marsden Hospital NHS Foundation Trust	London,
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	South Tees Hospitals NHS Foundation Trust of The James Cook University Hospital	Middlesbrough
United Kingdom	Norfolk and Norwich University Hospital NHS Trust	Norwich
United Kingdom	Nottingham University Hospitals, NHS Trust, Trust HQ, City Hospital	Nottingham
United Kingdom	Royal Cornwall Hospital NHS Trust	Truro	Cornwall
United Kingdom	MID & South Essex NHS Foundation Trust	Westcliff on Sea	Essex
United States	St. Luke's University Health Network - Allentown Cancer Center	Allentown	Pennsylvania
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Northside Hospital Atlanta	Atlanta	Georgia
United States	Northside Hospital Cancer Institute	Atlanta	Georgia
United States	University Hospitals Avon Health Center	Avon	Ohio
United States	MedStar Franklin Square Medical Center	Baltimore	Maryland
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	Nebraska Medicine - Bellevue	Bellevue	Nebraska
United States	St Luke's University Health Network, Bethlehem Campus	Bethlehem	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	University of Vermount and Sate Agricultural College	Burlington	Vermont
United States	Miami Valley Hospital South	Centerville	Ohio
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University Hospitals Geauga Medical Center	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Cincinnati	Cincinnati	Ohio
United States	Kaiser Sunnyside Medical Center	Clackamas	Oregon
United States	University Hospitals Cleveland Medical Centre	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Siteman Cancer Centre, Barnes Jewish West County	Creve Coeur	Missouri
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	St Luke's University Health Network, Anderson Campus	Easton	Pennsylvania
United States	Northwestern University	Evanston	Illinois
United States	Sanford Broadway Medical Centre	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Centre	Fargo	North Dakota
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	East Carolina University	Greenville	North Carolina
United States	Smilow Hospital Care Center, Guilford	Guilford	Connecticut
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Centre	Kalamazoo	Michigan
United States	University of Kansas Cancer Center	Kansas City	Missouri
United States	Northwestern Medicine Cancer Center Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Cooperman Barnabas Medical Center	Livingston	New Jersey
United States	The Angeles (Cedars-Sinai Medical Center and its Affiliates)	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Marshfield Medical Center - Marshfield	Marshfield	Wisconsin
United States	Aurora St Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Medical Center (Winthrop Hospital)	Mineola	New York
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Intermountain Medical Center	Murray	Utah
United States	Yale University	New Haven	Connecticut
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	VCU Massey Cancer Center Peninsula Cancer Institute	Newport News	Virginia
United States	Mercy Health Center - Oncology Hematology	Oklahoma City	Oklahoma
United States	OUHSC Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medicine	Omaha	Nebraska
United States	UC Irvine Health - Chao Family Comprehensive Cancer Center	Orange	California
United States	University Hospitals Chagrin Highlands Medical Centre	Orange Village	Ohio
United States	University of Kansas Hospital - Indian Creek Campus	Overland Park	Kansas
United States	Stanford Cancer Institute	Palo Alto	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	Rutgers Cancer Institute of New Jersey	Piscataway	New Jersey
United States	Kaiser Permanente Northwest - Oncology Clinic	Portland	Oregon
United States	Vassar Brothers Medical Center	Poughkeepsie	New York
United States	St Luke's University Health Network Quakertown Campus	Quakertown	Pennsylvania
United States	St. Luke's University Health Network - Upper Bucks	Quakertown	Pennsylvania
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	Carilion Roanoke Memorial Hospital	Roanoke	Virginia
United States	University of Rochester	Rochester	New York
United States	Huntsman Cancer Institute (The University of Utah)	Salt Lake City	Utah
United States	Univ of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Nancy N and JC Lewis Cancer & Research Pavilion St. Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Cox South Hospital	Springfield	Missouri
United States	State University of New York Upstate Medical Center-Community Campus	Syracuse	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Moffitt Cancer Center, Magnolia Campus	Tampa	Florida
United States	Kaiser Permanente - Vallejo Medical Center	Vallejo	California
United States	Kaiser Permanente - Walnut Creek Medical Center	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Wilmont Cancer Institute at Webster	Webster	New York
United States	West Chester Hospital (OH394)	West Chester	Ohio
United States	University Hospitals St. John Medical Center	Westlake	Ohio
United States	University of Kansas Hospital- Westwood Cancer Center	Westwood	Kansas
United States	VCU Massey Cancer Center Affiliate Valley Health	Winchester	Virginia

Sponsors (5)

Lead Sponsor	Collaborator
Melanoma and Skin Cancer Trials Limited	Canadian Cancer Trials Group, Cancer Trials Ireland, Norfolk and Norwich University Hospitals NHS Foundation Trust, Zuyderland Medical Centre

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy,  Netherlands,  New Zealand,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival	Time from randomisation to clinically, histologically or radiologically confirmed recurrence of melanoma	0-60 months
Secondary	Local Recurrence	Time from randomisation to any clinically, histologically or radiologically confirmed local recurrence of melanoma including satellite lesions and in transit metastases to regional draining lymph nodes	Day 0-Trial Completion (max. 120 months)
Secondary	Distant Disease-Free Survival	Time from randomisation to any clinically, histologically or radiologically confirmed distant recurrence of melanoma	Day 0-Trial Completion (max. 120 months)
Secondary	Melanoma-Specific Survival	Time from randomisation to death due to melanoma	Day 0-Trial Completion (max. 120 months)
Secondary	Overall Survival	Time from randomisation to death from any cause	Day 0-Trial Completion (max. 120 months)
Secondary	Melanoma-specific Quality of Life: FACT-M questionnaire	Measured by FACT-M (Functional Assessment of Cancer Therapy - Melanoma) questionnaire - It consists of two subsections: The FACT-G subsection is a 27-item compilation of general questions divided into four primary QOL domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. It is considered appropriate for use with patients with any form of cancer. The Melanoma Surgery Subscale evaluates melanoma-specific symptoms such as surgical morbidity and side effects.	Baseline, 3, 6, 12 & 24 months
Secondary	Neuropathic Pain: PainDetect questionnaire	Measured by PainDetect questionnaire	Baseline, 3, 6, 12 & 24 months
Secondary	Health-related Quality of Life: EQ-5D-5L questionnaire	Measured by EuroQoL EQ-5D-5L questionnaire - This tool contains 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression.	Baseline, 3, 6, 12 & 24 months
Secondary	Surgery Related Adverse Events	The following surgical adverse events will be recorded from the time of surgery to 90 days following surgery (inclusive): wound dehiscence; seroma/haematoma; haemorrhage; infection; skin graft failure; necrosis of flap used for reconstruction; deep venous thrombosis; urinary tract infection; pneumonia; cardiac complications; lymphoedema	Up to 90 days from the date of surgery
Secondary	Adverse Events	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a treatment which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the treatment timing, whether or not considered related to the treatment. An AE is any adverse change (developing or worsening) from the participant's pre-treatment condition, including intercurrent illness.	Within 1 year from randomisation
Secondary	Health Economic Evaluation	Data collected for economic analysis will be from hospital notes, MBS and PBS data (Australia) and patient reported outcome measures (including an employment questionnaire) at baseline, 3, 6, 12 and 24 months and at melanoma recurrence.	Baseline, 3, 6, 12 & 24 months