Evaluation of Groin Lymphadenectomy Extent For Metastatic Melanoma

NCT02166788 | Completed Phase 3 DMC

• 1 other identifier: 01.12
• Study Type: interventional
• Target: 634
• Locations: 6 countries
• Sites: 17

Brief Summary

BACKGROUND: Spread of metastatic melanoma to the groin lymph nodes (LN) is a common event affecting about 350 people a year in Australia. Globally it has been shown that patients with involved groin LN, without proven pelvic LN disease on imaging receive 1 of 3 management strategies in equal proportions - inguinal lymphadenectomy (IL); ilio-inguinal lymphadenectomy (I-IL); or variable use of either depending on circumstances. Different experts have strong and polarised opinions favouring either IL or more extensive I-IL with existing cases series reporting conflicting data on best cancer outcomes. No high level evidence proves which operation is best. HYPOTHESIS: There will be no significant difference in DFS between patients having IL or I-IL, conditional on PET/CT scan showing no evidence of pelvic disease at the time of diagnosis of groin LN metastatic melanoma. AIMS: To provide a rational evidence base for management for melanoma to the groin LNs by randomly assessing the effect of each operation on DFS, distant DFS, overall survival (OS), morbidity - including early complications and longer-term rates of lymphedema as well as comprehensively assessed QOL. Also to clarify the reliability of PET/CT scans for staging pelvic LNs and evaluate any health economic benefits of I-IL over IL. TARGET POPULATION: To recruit 634 patients in 5 years. DESIGN: An Australian led, international, multi-centre, non-inferiority, phase III, prospective, randomised clinical trial comparing IL or I-IL for patients with metastatic melanoma to groin LNs and no evidence of pelvic disease on PET/CT. ENDPOINTS: DFS, Distant DFS, OS and QOL at 5 years. Accuracy of PET/CT for pelvic LN metastases. OUTCOMES: International standardization of care, improved cancer outcomes, improved QOL for patients with groin metastatic melanoma. Proof of principle about extent of surgery when PET/CT is clear in adjacent LN areas, leading to clinical trials investigating management of other lymph node fields.

Conditions

Metastatic Melanoma to the Groin Lymph Nodes

Keywords

metastatic melanoma; groin lymph nodes; surgery; lymphadenectomy

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the study will be Disease Free Survival following lymphadenectomy, assessed after 60 months of follow-up.

  The difference between IL and I-IL surgery in DFS 5 years after randomisation

  60 Months

Secondary Outcomes (7)

• Overall Survival

  0 - 120 months

• Distant Disease Free Survival

  0 - 120 Months

• Regional Recurrence Free Survival

  0 - 120 Months

• Morbidity differences

  Up to 120 days from lymphadenectomy, and from 0 - 120 months

• Quality Of Life

  0 - 120 Months

Study Arms (2)

Arm 1: Inguinal Lymphadenectomy

OTHER

Inguinal Lymphadenectomy (IL) is removal of the easily accessible superficial groin lymph nodes (LNs) and has a median LN retrieval of 11 lymph nodes

Procedure: Inguinal Lymphadenectomy

Arm 2: Ilio-inguinal Lymphadenectomy

OTHER

Ilio-inguinal Lymphadenectomy (I-IL) is the removal of the same superficial groin lymp nodes (LN) removed during an IL but also combined with the more surgically complex removal of the ipsilateral pelvic LN. About twice as many LN are removed with I-IL compared to IL.

Procedure: Ilio-inguinal Lymphadenectomy

Interventions

Inguinal Lymphadenectomy PROCEDURE

Arm 1: Inguinal Lymphadenectomy

Ilio-inguinal Lymphadenectomy PROCEDURE

Arm 2: Ilio-inguinal Lymphadenectomy

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be included in the study only if they meet all of the following criteria:
• Must be 15 and above.
• Have primary cutaneous melanoma or if the patient presents with stage III melanoma with no known primary tumour then a thorough search for the primary should be documented (including perineal and perianal areas)
• Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI
• Must have one or multiple inguinal node(s) involved, histologically or cytologically proven as metastatic melanoma. This can can be detected:
• At the time of diagnosis;
• Or by Ultrasound detection;
• Or later after relapse when no Sentinel Node Biopsy (SNB) was performed at the time of primary tumour management;
• Or as a result of SNB;
• Or at the time of regional recurrence after "false negative" SNB;
• Absent distant disease clinically and on PET/CT scan. (Patients must have NO further distant disease or visceral metastases)
• ECOG performance status must be between 0 to 2 at randomisation
• Whole body PET/CT scan, specifically stating there is NO evidence of pelvic lymph node involvement prior to randomisation and a CT Brain or MRI Brain scan. Scans must be performed within 6 weeks prior to randomisation.
• Able to provide written, informed consent
• Willing to return to the centre for follow up examinations and procedures, as outlined in the protocol.

You may not qualify if:

• Distant metastatic disease on clinical examination or staging imaging (CT/MRI brain or whole body PET/CT scan). Scans must be performed within 6 weeks prior to randomisation
• Pelvic LN involvement on SNB or PET/CT scan suggestive of metastatic disease in the pelvis - criteria for diagnosis include normal size or enlarged lymph nodes (\> 1 cm) with increased FDG activity on PET (SUV \>3). If there are enlarged, necrotic lymph nodes FDG activity on PET is not required to be present. If unsure central review should be sought.
• Bilateral inguinal lymph node involvement
• Patients with a history of major pelvic surgery and / or regional radiotherapy at any time in the past
• Requiring planned radiotherapy following surgery due to macroscopic, bulky and matted nodes.
• Unfit for General Anaesthesia
• Melanoma-related operative procedures not corresponding to criteria described in the protocol
• Patients with prior cancers, except:
• those with a thin \<=1 mm, regionally unrelated melanoma \> 5 years ago
• those with a good prognosis regionally unrelated cancer (\>90% probability of 10 years disease specific survival)
• other cancers diagnosed more than five years ago with no evidence of disease recurrence within this time
• successfully treated basal cell and squamous cell skin carcinoma
• carcinoma in-situ of the cervix
• episode of in transit melanoma \> 3 years ago
• A medical or psychiatric condition that compromises ability to give informed consent or complete the protocol

Sponsors & Collaborators

• Melanoma and Skin Cancer Trials Limited: lead
• Cancer Council New South Wales: collaborator
• Melanoma Institute Australia: collaborator

Study Sites (17)

Calvary Public Hospital Bruce

Canberra, Australian Capital Territory, 2617, Australia

Location

Melanoma Institute Australia - The Poche Centre

North Sydney, New South Wales, 2060, Australia

Location

Sydney Adventist Hospital

Sydney, New South Wales, 2076, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Location

Mater Hospital Brisbane

Brisbane, Queensland, 4101, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

A.C. Camargo Cancer Center

São Paulo, São Paulo, 01508-010, Brazil

Location

Veneto Institute of Oncology - IOV

Padua, Veneto, 35128, Italy

Location

Radboud University Nijmegen Medical Center

Nijmegen, Gelderland, 6525, Netherlands

Location

University Medical Center Groningen

Groningen, Provincie Groningen, 9713, Netherlands

Location

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location

Norfolk and Norwich University Hospital

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Guy's and St Thomas's Hospitals

London, United Kingdom

Location

St George's Hospital

London, United Kingdom

Location

St Helen's and Knowsley Teaching Hospitals

St Helens, United Kingdom

Location

Related Publications (1)

• Mahumud RA, Law CK, Ospino DA, de Wilt JHW, van Leeuwen BL, Allan C, de Lima Vazquez V, Jones RP, Howle J, Peric B, Spillane AJ, Morton RL. Economic Evaluation of Inguinal Versus Ilio-inguinal Lymphadenectomy for Patients with Stage III Metastatic Melanoma to Groin Lymph Nodes: Evidence from the EAGLE FM Randomized Trial. Ann Surg Oncol. 2025 Jun;32(6):4211-4222. doi: 10.1245/s10434-025-17040-2. Epub 2025 Feb 27.

  PMID: 40016616 DERIVED

Related Links

• Trial Website

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andrew Spillane

  The University of Sydney, Northern Clinical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2014
• First Posted: June 18, 2014
• Study Start: March 2, 2015
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: May 9, 2025

Record last verified: 2022-04

Locations

AU (7); NL (2); BR (2); IT (1); SL (1); GB (4)