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Trial registered on ANZCTR


Registration number
ACTRN12614000667617
Ethics application status
Approved
Date submitted
6/06/2014
Date registered
25/06/2014
Date last updated
19/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase III, multi-centre, multi-national randomised control trial investigating 1cm v 2cm wide excision margins for primary cutaneous melanoma.
Scientific title
A Phase III, multi-centre, multi-national randomised control trial investigating 1cm v 2cm wide excision margins for primary cutaneous melanoma on disease recurrence and survival.
Secondary ID [1] 284751 0
ANZMTG 03.12
Universal Trial Number (UTN)
Trial acronym
MelMarT - Melanoma Margins Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Melanoma 292119 0
Condition category
Condition code
Cancer 292453 292453 0 0
Malignant melanoma
Surgery 292488 292488 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of the primary lesion for adult patients with a primary invasive cutaneous melanomas >=1mm thick to determine differences in the rate of local recurrence and melanoma specific survival.

ARM A: Experimental Arm
Wide Local Excision = 1cm Margin
+ Sentinel Lymph Node Biopsy
+/- Reconstruction
These procedures need to be performed +<14 days from the date of randomisation.
Intervention code [1] 289541 0
Treatment: Surgery
Comparator / control treatment
ARM B:Control Arm
Wide Local Excision = 2cm Margin
+ Sentinel Lymph Node Biopsy
+/- Reconstruction
These procedures need to be performed +<14 days from the date of randomisation.
Control group
Active

Outcomes
Primary outcome [1] 292314 0
Local Melanoma Recurrence
Timepoint [1] 292314 0
Time from randomisation to confirmed local recurrence of melanoma 0-120 months
Primary outcome [2] 292350 0
Melanoma Specific Survival
Timepoint [2] 292350 0
Time from randomisation to death due to melanoma 0-120 months
Secondary outcome [1] 308702 0
Recurrence-Free Survival
Timepoint [1] 308702 0
Time from randomisation to confirmed melanoma recurrence or death from any cause 0-120 months
Secondary outcome [2] 308703 0
Quality of life (QOL)
assessed via;
FACT-M, EQ-5D-5L Questionnaires, PainDetect Questionnaire (neuropathic pain assessment)
Timepoint [2] 308703 0
Baseline, 3, 6, 12, 24 and 60 months and at melanoma recurrence
Secondary outcome [3] 308748 0
Overall Survival
Timepoint [3] 308748 0
Time from randomisation to death from any cause 0-120 months
Secondary outcome [4] 308750 0
Surgery Related Adverse Events The following surgical adverse events will be recorded from the time of trial treatment to 30 days following the wide excision (inclusive): * wound separation * seroma/haematoma at wide local excision site * haemorrhage * infection * skin graft failure * necrosis of flap used for reconstruction * deep venous thrombosis * urinary tract infection * pneumonia * cardiac complications Surgical adverse events will be graded in severity according to the Clavien-Dindo system
Timepoint [4] 308750 0
Up to 30 days following the Wide Local Excision
Secondary outcome [5] 308776 0
Adverse Events
AE's are recorded for all patients on trial at Baseline assessment and routinely throughout follow up
Timepoint [5] 308776 0
0-12 months

Eligibility
Key inclusion criteria
1 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.
2 Must have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm, sole).
3 An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary melanoma.
4 Randomisation and the primary study intervention, including staging sentinel node biopsy, must be completed by 120 days of 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 10 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.
Minimum age
18 Years
Maximum age
120 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.
5 Microsatellitosis as per AJCC 2009 definition
6 Subungual melanoma
7 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.
8 History of previous or concurrent (i.e., second primary) invasive melanoma.
9 Melanoma located distal to the metacarpophalangeal joint, on the tip of the nose, the eyelids or on the ear, mucous membranes or internal viscera.
10 Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic melanoma.
11 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.
12 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.
13 Melanoma-related operative procedures not corresponding to criteria described in the protocol.
14 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.
15 History of organ transplantation.
16 Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at any time during study participation or within 6 months prior to enrolment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation of treatment will be performed centrally via an online randomisation system. Sites will be notified as to which arm treatment the patient was allocated via email.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a randomised controlled clinical trial.
This study will use a Permuted block randomisation method for the allocation of subjects into different groups.
Randomisation according to stratification factors: Risk Group, Age, Sex, Site.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 2607 0
The Poche Centre, Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 2608 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [3] 8011 0
The Alfred - Prahran
Recruitment hospital [4] 8012 0
Gold Coast Melanoma Clinic - Coolangatta
Recruitment postcode(s) [1] 8280 0
2060 - North Sydney
Recruitment postcode(s) [2] 15990 0
3002 - East Melbourne
Recruitment postcode(s) [3] 15991 0
3004 - Prahran
Recruitment postcode(s) [4] 15992 0
4225 - Coolangatta
Recruitment outside Australia
Country [1] 6102 0
United Kingdom
State/province [1] 6102 0
England
Country [2] 8896 0
Canada
State/province [2] 8896 0
Ontario
Country [3] 8897 0
United States of America
State/province [3] 8897 0
Pennsylvania
Country [4] 8898 0
Sweden
State/province [4] 8898 0
Gothenburg

Funding & Sponsors
Funding source category [1] 289369 0
Charities/Societies/Foundations
Name [1] 289369 0
Cancer Council NSW
Address [1] 289369 0
153 Dowling Street, Woolloomooloo NSW 2011
PO Box 572, Kings Cross NSW 1340

Country [1] 289369 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Melanoma Trials Group (ANZMTG)
Address
ANZMTG
The Poche Centre
40 Rocklands Road,
North Sydney, NSW 2060
Australia
Country
Australia
Secondary sponsor category [1] 288054 0
Other Collaborative groups
Name [1] 288054 0
Melanoma Institute Australia
Address [1] 288054 0
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country [1] 288054 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291135 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 291135 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Ethics committee country [1] 291135 0
Australia
Date submitted for ethics approval [1] 291135 0
18/07/2014
Approval date [1] 291135 0
28/10/2014
Ethics approval number [1] 291135 0

Summary
Brief summary
This study will determine whether there is a difference in local recurrence rates and melanoma survival rates for patients treated with either a 1cm excision margin or 2cm margin for both intermediate & high risk melanomas.

Who is it for?
You may be eligible to participate in this study if you are aged 18 years or above and have been diagnosed with a primary invasive cutaneous melanoma greater than 1mm in thickness.

Study details:
Whilst patients with a primary invasive melanoma are generally 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. Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will undergo surgery with the 2cm excision margin, whilst participants in the other group will undergo surgery with a 1cm excision margin.

Participants will be monitored for up to 120 months, in order to determine melanoma recurrence, survival rates and quality of life, and additionally, adverse events and health resource usage.
Trial website
http://www.anzmtg.org/trialdetails.aspx?trialno=14
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49030 0
Prof Michael Henderson
Address 49030 0
Peter MacCallum Cancer Centre
Division of Cancer Surgery
Peter MacCallum Cancer Centre, 7 St Andrew's Place
East Melbourne, VIC 3002
Country 49030 0
Australia
Phone 49030 0
+6 13 9656 3527
Fax 49030 0
+6 13 9654 8457
Email 49030 0
Michael.Henderson@petermac.org
Contact person for public queries
Name 49031 0
Mr ANZMTG Coordinator
Address 49031 0
ANZMTG Australia and New Zealand Melanoma Trials Group
The Poche Centre
40 Rocklands Road
North Sydney NSW 2060
Country 49031 0
Australia
Phone 49031 0
+61 2 9911 7329
Fax 49031 0
+61 2 9954 9290
Email 49031 0
MELMART@melanoma.org.au
Contact person for scientific queries
Name 49032 0
Mr ANZMTG Coordinator
Address 49032 0
ANZMTG Australia and New Zealand Melanoma Trials Group
The Poche Centre
40 Rocklands Road
North Sydney NSW 2060
Country 49032 0
Australia
Phone 49032 0
+61 2 9911 7329
Fax 49032 0
+61 2 9954 9290
Email 49032 0
MELMART@melanoma.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary