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