NCT07049276

The Multicentre Selective Lymphadenectomy Trial - 3

Randomized Controlled Trial of Selective Index Lymph Node Resection Versus Therapeutic Lymph Node Dissection After Neoadjuvant Immunotherapy for Stage IIIB-D Melanoma

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,500 (estimated)
• Sponsor: Melanoma Institute Australia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The standard treatment under current guidelines for patients who have melanoma that has spread to the lymph nodes (Stage III disease) is a 'therapeutic lymph node dissection' or 'TLND'. This is the removal of all of the lymph nodes in the affected area, such as in the armpit, neck or groin. TLND surgery Several clinical trials over the past 10 to 15 years have shown that treatment with immune system boosting drugs (known as immunotherapy) can help the body to better identify and attack the tumour cells. This is now used routinely for tumour that has spready beyond the lymph nodes (Stage IV disease) in melanoma and many other cancers. When immunotherapy is given before TLND surgery (known as neoadjuvant therapy) the body can launch an increased immune response against the tumour cells to reduce or remove the amount of tumour before surgery. Neoadjuvant therapy for melanoma is typically given over 6 weeks before surgery. Patients may have further drug therapy and /or radiotherapy after TLND surgery to minimise the risk of recurrence. At surgery after neoadjuvant immunotherapy, the removed lymph node tissue is examined by a pathologist who will then classify the amount of tumour cells left in the lymph nodes. Recent clinical trials have shown that 46-70% of patients have less than 10% of melanoma cells left in the lymph nodes. This is called a 'major pathological response' or 'MPR'. After 5 years, approximately 70% of patients having an MPR do not have a recurrence of melanoma. Neoadjuvant immunotherapy is now standard care for Stage III melanoma in Australia and other countries. Both immunotherapy and TLND surgery have side effects. Some of these are of short duration and some last many months. Some of the side effects from immunotherapy include general nausea, diarrhoea, skin rash but also diabetes, thyroid or liver problems. Surgery may result in some pain, wound infection, wound breakdown, or short and long term lymphoedema - where fluid doesn't drain properly from the arms or legs, depending on where the original lymph node surgery was done. A recent small clinical trial of 99 patients tested if patients who have neoadjuvant therapy can omit the need for TLND surgery, without changing the risk of recurrence. Patients in this study had the largest affected (index) lymph node marked with a clip under ultrasound or X-ray guidance before neoadjuvant therapy. After 6 weeks of neoadjuvant immunotherapy, the index lymph node was removed in a minor operation and the pathological response classified. Sixty-one percent of patients had an MPR and did not have any further surgery. After 2 years, 93% of these patients did not have a recurrence of melanoma. Patients without an MPR had TLND surgery and between 63 and 75% had no recurrence by 2 years. This recent trial was too small to provide sufficient evidence for a change in standard treatment after neoadjuvant immunotherapy for patients having an MPR. We therefore plan to conduct a trial that is large enough to test if the new approach of index lymph node resection is not worse than the current standard care with TLND as measured by the number of people without melanoma recurrence within 2 years. This type of trial is known as a 'non-inferiority' trial. If index node resection is no worse than TLND, we also need to assess if there is a difference in the side effects or each type of surgery and in the quality of life experienced by patients. We also need to examine if there is any difference in the costs to patients and to the healthcare system for either surgery and the long term outcomes. This is a randomised trial which means people are put into one of two groups by chance (randomly, or like tossing a coin). For patients who have an MPR to neoadjuvant therapy, half will have index lymph node removal with no further surgery and half the current standard of TLND surgery. Patients who do not have an MPR will have the standard TLND. All patients will have regular appointments with their surgeon to check for signs if the melanoma has returned and the study team will follow progress for up to 10 years.

Conditions

• Cutaneous Melanoma, Stage III

Interventions

Type	Name	Description
PROCEDURE	Index lymph node resection	The largest lymph node affected with melanoma
PROCEDURE	Therapeutic lymph node dissection	Removal of all nodes in the melanoma affected lymph node basin

Timeline

• Start date: 2025-10-01
• Primary completion: 2030-08-01
• Completion: 2040-08-01
• First posted: 2025-07-03
• Last updated: 2026-02-18

Locations

6 sites across 6 countries: United States, Australia, Canada, Italy, New Zealand, United Kingdom