The Multicentre Selective Lymphadenectomy Trial - 3

NCT07049276 | Recruiting DMC

• 1 other identifier: MIA2024/501
• Study Type: interventional
• Target: 1,500
• Locations: 5 countries
• Sites: 7

Brief Summary

The goal of this clinical trial is to demonstrate that there is no difference (non-inferiorty) in the 2 year recurrence-free survival (RFS) between 2 different surgical approaches for clinical Stage III melanoma. Following 6 weeks of standard neaodjuvant immunotherapy, patients will undergo either selective index lymph node resection (ILN) (identified at baseline as the largest affected lymph node) or the standard of care therapeutic lymph node dissection (TLND). The secondary aims are to assess if patients who are managed without TLND will have a reduction in surgical complications (less wound problems \& lymphoedema), an improved quality of life, at a lower healthcare utilisation.

Conditions

Cutaneous Melanoma, Stage III

Keywords

Neoadjuvant; Non-inferiority; Randomised controlled trial; Adverse events; Quality of life; Healthcare economics; Index lymph node resection; Therapeutic lymph node dissection; Surgical morbidity

Outcome Measures

Primary Outcomes (1)

• Recurrence free survival

  The proportion of patients with a major pathological response (MPR) alive and disease-free from the time of surgery to the end of 2 years follow up

  2 years

Secondary Outcomes (13)

• The rate of escalation to a therapeutic lymph node dissection (TLND) in the ILN arm due to isolated nodal recurrence in the ILN nodal basin

  2 years

• The salvage rate with surgery, radiotherapy or new systemic therapy post operatively for disease recurrence in each surgical arm with a major pathological response (complete pathological response or near complete pathological response)

  2 years

• Distant metastasis free-survival

  2 years

• Overall survival

  10 years

• Surgery-related adverse events

  2 years

Other Outcomes (1)

• To identify prognostic and predictive biomarkers for recurrence

  2 years

Study Arms (2)

Index Lymph Node

EXPERIMENTAL

The largest affected (index) lymph node marked with a clip under ultrasound or X-ray guidance and then removed after neoadjuvant therapy for the pathological response to be determined. The response then dictates the next step of management

Procedure: Index lymph node resection

Therapeutic lymph node dissection

ACTIVE COMPARATOR

Complete removal of all nodes in the regional lymph node basin

Procedure: Therapeutic lymph node dissection

Interventions

Index lymph node resection PROCEDURE

The largest lymph node affected with melanoma

Index Lymph Node

Therapeutic lymph node dissection PROCEDURE

Removal of all nodes in the melanoma affected lymph node basin

Therapeutic lymph node dissection

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years of age at the time of consent
• Written informed consent
• Cytologically or histologically confirmed, resectable pathological Stage IIIB, C or D (Any T, N1b, N2b, N2c, N3b, or N3c) cutaneous or unknown primary melanoma, with or without primary tumour in situ
• A minimum of one macroscopic lymph node, defined as:
• A palpable node, confirmed by pathology
• A non-palpable node, but enlarged per RECIST 1.1 criteria (≥ 15 mm in shortest diameter) and confirmed by pathology
• An ultrasound or PET/CT scan positive lymph node of any size, confirmed by pathology.
• Up to 3 satellite (defined as any foci of clinically evident cutaneous and/or subcutaneous metastases occurring within 2 cm of but discontinuous from the primary melanoma) or in-transit metastases (defined as clinically evident cutaneous and/or subcutaneous metastases occurring \>2 cm from the primary melanoma in the region between the primary and the regional lymph node basin) are permitted if they are completely resectable.
• Lymph node involvement in the groin (iliac, inguinal or both), axilla or neck only and may be unilateral or bilateral. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
• Tumour amenable to a newly obtained core biopsy of a lesion which has not been previously irradiated. Archival tissue from a past primary or nodal lesion (if applicable) or tissue taken for current diagnosis will also be collected if available.
• Systemic neoadjuvant immunotherapy is scheduled for administration with at least one PD-(L)-1 check point inhibitor (e.g. nivolumab, pembrolizumab, cemiplimab). The immunotherapy regimen may include other checkpoint inhibitors (e.g. ipilimumab, relatlimab, fianlimab). The patient should meet the fitness for treatment requirements as detailed in the relevant regulatory-approved Product Information or Summary of Product Characteristics.
• Neoadjuvant course of treatment to be no longer than 6 weeks (allows for a maximum of 3 cycles at weeks 0, 3 and 6).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Anticipated life expectancy of \> 5 years.

You may not qualify if:

• Uveal or mucosal melanoma.
• Isolated satellite or in-transit metastases only (without any cytological or histological proven lymph node involvement).
• Involvement of any lymph node basin other than groin, axilla or neck. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
• Clinical or radiographic evidence of distant metastasis (any AJCC 8th ed M Stage).
• Previous history of lymph node surgery to the same nodal basin, that was more extensive than a sentinel lymph node biopsy (SLNB).
• Previous radiotherapy to the same nodal basin.
• Any contraindication to the administration of nivolumab, ipilimumab, pembrolizumab or relatlimab per regulatory-approved product information and / or medical oncologist.
• Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment.
• A plan to administer targeted therapy or any non-checkpoint inhibitor immunotherapy, or any intralesional therapy for melanoma in the neoadjuvant setting.
• A plan to administer any experimental immunotherapy as part of a clinical trial in the neoadjuvant setting.
• Known additional malignancies (unless adequately treated) active within the previous 3 years, except for locally curable cancers that have been apparently cured. The following malignancies, if undergone successful definitive resection or curative treatment, are permitted:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, but excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy
• Prostatic intraepithelial neoplasia

Sponsors & Collaborators

• Melanoma Institute Australia: lead

Study Sites (7)

Cedars-Sinai Medical Centre

Los Angeles, California, 90025, United States

NOT YET RECRUITING

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6961, Australia

NOT YET RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

NOT YET RECRUITING

San Maria della Misericordia Hospital

Perugia, Italy

NOT YET RECRUITING

The Royal Marsden

London, United Kingdom

NOT YET RECRUITING

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

• Alexander CJ van Akkooi

  Melanoma Institute Australia

  STUDY CHAIR

Central Study Contacts

Alexander CJ van Akkooi

CONTACT

+612 9911 7200; alexander.vanakkooi@melanoma.org.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Non-inferiority

Study Record Dates

• First Submitted: May 24, 2025
• First Posted: July 3, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2040
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

CA (1); AU (3); US (1); IT (1); GB (1)