Evaluation of Groin Lymphadenectomy Extent For Metastatic Melanoma

NCT ID: NCT02166788

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 634 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-02
• Study Completion Date: 2024-10-17

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.

Detailed Description

Background and Rationale

Spread of metastatic melanoma to the groin lymph nodes (LN) is a common event for patients with melanoma. In melanoma treatment centres around the world, patients without demonstrated pelvic LN disease receive 1 of 3 strategies of management in relatively equal proportions (Pasquali, Spillane et al. 2012):

i. Inguinal Lymphadenectomy (IL) ii. Ilio-inguinal Lymphadenectomy (I-IL) iii. Variable use of either IL or I-IL surgery.

Some larger melanoma centres have an institutional policy that all patients have either IL or I-IL for metastatic inguinal node involvement. Nearly all centres would agree that patients with pelvic LN involvement without distant metastatic disease should have I-IL.

Study Objectives This study aims to provide a more rational evidence base for appropriate management for metastatic melanoma in the groin LNs, through assessing the effect of the addition of ipsilateral pelvic lymphadenectomy on patient disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), morbidity, and quality of life. In addition, the study will clarify the reliability of PET (Positron Emission Tomography) / CT (Computed Tomography) scans for staging pelvic LNs, clarify morbidity differences between the operations in a balanced cohort, evaluate any health economic benefits of I-IL over IL and provide a tissue and serum resource to be used to identify biological markers of recurrence and progression after inguinal metastases.

Study 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.

Study Population The aim is to recruit 634 patients in 5 years who are 15 years or older with cytologically or histologically confirmed metastatic melanoma in inguinal LNs (H&E & IHC); specifically with no evidence of pelvic node involvement or distant spread of melanoma clinically or on PET/CT staging scans. To be eligible patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 at randomisation.

Study Treatments Eligible patients will be randomised 1:1 to undergo an IL or I-IL.

Study Design This is an international, multi-centre, phase III, non-inferiority, prospective, randomised clinical trial.

Conditions

Metastatic Melanoma to the Groin Lymph Nodes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Inguinal Lymphadenectomy

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

Group Type: OTHER

Inguinal Lymphadenectomy

Intervention Type: PROCEDURE

Arm 2: Ilio-inguinal Lymphadenectomy

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.

Group Type: OTHER

Ilio-inguinal Lymphadenectomy

Intervention Type: PROCEDURE

Interventions

Inguinal Lymphadenectomy

Intervention Type: PROCEDURE

Ilio-inguinal Lymphadenectomy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

Patients may be included in the study only if they meet all of the following criteria:

1. Must be 15 and above.

2. 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)

3. Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI

4. 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;

5. Absent distant disease clinically and on PET/CT scan. (Patients must have NO further distant disease or visceral metastases)

6. ECOG performance status must be between 0 to 2 at randomisation

7. 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.

8. Able to provide written, informed consent

9. Willing to return to the centre for follow up examinations and procedures, as outlined in the protocol.

10. All patients must be randomised and undergo lymphadenectomy surgery no more than 120 days following diagnosis of inguinal LN involvement

Exclusion Criteria

1. 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

2. 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.

3. Bilateral inguinal lymph node involvement

4. Patients with a history of major pelvic surgery and / or regional radiotherapy at any time in the past

5. Requiring planned radiotherapy following surgery due to macroscopic, bulky and matted nodes.

6. Unfit for General Anaesthesia

7. Melanoma-related operative procedures not corresponding to criteria described in the protocol

8. 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
• 1 episode of in transit melanoma > 3 years ago

9. A medical or psychiatric condition that compromises ability to give informed consent or complete the protocol

10. Positive urine pregnancy test for women of childbearing potential (+/-7 days of randomisation onto the trial)

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Council New South Wales

OTHER

Sponsor Role: collaborator

Melanoma Institute Australia

OTHER

Sponsor Role: collaborator

Melanoma and Skin Cancer Trials Limited

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Spillane

Role: PRINCIPAL_INVESTIGATOR

The University of Sydney, Northern Clinical School

Locations

Calvary Public Hospital Bruce

Canberra, Australian Capital Territory, Australia

Melanoma Institute Australia - The Poche Centre

North Sydney, New South Wales, Australia

Sydney Adventist Hospital

Sydney, New South Wales, Australia

Westmead Hospital

Sydney, New South Wales, Australia

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Mater Hospital Brisbane

Brisbane, Queensland, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

A.C. Camargo Cancer Center

São Paulo, São Paulo, Brazil

Veneto Institute of Oncology - IOV

Padua, Veneto, Italy

Radboud University Nijmegen Medical Center

Nijmegen, Gelderland, Netherlands

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Norfolk and Norwich University Hospital

Norwich, Norfolk, United Kingdom

Guy's and St Thomas's Hospitals

London, , United Kingdom

St George's Hospital

London, , United Kingdom

St Helen's and Knowsley Teaching Hospitals

St Helens, , United Kingdom

Countries

Australia; Brazil; Italy; Netherlands; Slovenia; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40016616 (View on PubMed)

Related Links

https://www.masc.org.au/

Trial Website

Other Identifiers

01.12

Identifier Type: -

Identifier Source: org_study_id