Omitting Therapeutic Lymph Node Dissection in Patients With Melanoma (Stage 3) and Major Pathological Response in the Index Lymph Node (OMIT)

D.J. (Dirk) Grünhagen

Status

Enrolling

Conditions

Melanoma, Skin

Treatments

Procedure: Omitting TLND

Procedure: Index node procedure

Study type

Interventional

Funder types

Other

Identifiers

NCT06754904

NL88017.078.24 (Registry Identifier)

Details and patient eligibility

About

Rationale: The randomized trial NADINA has demonstrated that neoadjuvant treatment with nivolumab with ipilimumab improves event-free survival (EFS) in patients with macroscopic resectable stage III melanoma. In this study, therapeutic lymph node dissection (TLND) was standard of care, showing that patients achieving a major pathological response (MPR, i.e., ≤10% residual viable tumor bed) have an excellent outcome (EFS and Distant Metastasis Free Survival (DMFS)). The PRADO trial indicated that the MPR definition can also be revealed from a surrogate lymph node response, the index lymph node (ILN), allowing sparing the extensive surgery in MPR patients. In these MPR patients the DMFS was 100% after 1 year and 98% after 2 years, and recurrence-free survival (RFS) was 95% after 1 year and 93% after 2 years. Given that TLND is associated with morbidity and has a significant impact on health-related quality of life (HR-QoL) and healthcare costs, this study aims to prospectively investigate the safety of omitting TLND in patients who have an MPR within the ILN after neoadjuvant immunotherapy.

Objectives: To investigate whether TLND can be safely omitted in patients with macroscopic resectable stage III (B/C/D) melanoma achieving an MPR within the ILN upon neoadjuvant treatment with immune checkpoint inhibitors (ipilimumab and nivolumab).

Study design: This study is a prospective, single-arm phase 2 nationwide multicenter trial.

Study population:

Inclusion criteria for study participants are as follows:

Patients must be eligible for neoadjuvant treatment
Patients must have a histologically confirmed diagnosis of macroscopic resectable stage III melanoma (stage III B/C/D) with one or more macroscopic lymph node metastasis
The patient must have a measurable tumor burden that qualifies (according to clinical practice) for neoadjuvant therapy

Intervention: Omitting TLND in patients who achieve an MPR in the ILN following neoadjuvant ipilimumab and nivolumab.

Main study endpoints: The two coprimary endpoints are 2-year Local Recurrence Free Survival (LRFS) and 2-year DMFS.

Enrollment

213 estimated patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients must be eligible for neoadjuvant treatment (ipilimumab and nivolumab)
Patients must be 16 years of age or older.
Patients must have a histologically confirmed diagnosis of macroscopic resectable stage III melanoma (stage III B/C/D) with one or more macroscopic lymph node metastase defined as either one:
a palpable node, confirmed as melanoma by pathology; a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis), confirmed as melanoma by pathology;
a PET scan positive lymph node of any size confirmed as melanoma by pathology;
The patient must have a measurable tumor burden that qualifies (according to clinical practice) for neoadjuvant therapy with immune checkpoint inhibitors
Patients in whom ILN marking is feasible
Written informed consent

Exclusion criteria

Uveal/ocular or mucosal melanoma
WHO performance status of two or more
In-transit metastases only (without cytological or histological proven lymph node involvement)
Prior targeted therapy targeting BRAF and/or MEK for melanoma
Prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 for melanoma
Patients with (history of) distant metastasis (stage IV melanoma)