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NCT Number: NCT06754904

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

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.

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Key information

Conditions

Melanoma, Skin Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Omitting TLND

Procedure

Omitting TLND in patients who achieve an MPR in the index node following neoadjuvant ipilimumab and nivolumab.

Index node procedure

Procedure

Index node procedure

Primary outcomes

  1. Local Recurrence Free Survival (LRFS)

    Time frame: 2 years after inclusion

    LRFS, as defined as time from removal of the index lymph node (ILN) until local (in basin) recurrence in the MPR group. Accepting a local relapse of 20%.

  2. Distant Metastasis Free Survival (DMFS)

    Time frame: 2 years after inclusion

    DMFS assessed in the MPR group, as defined as time from the start of neoadjuvant immunotherapy, nivolumab with ipilimumab, until the first occurrence of distant metastasis. Accepting DMFS 3% lower than the 2 years DMFS of the NADINA trial

Secondary outcomes

  1. Evaluation of health-related quality of life (HRQoL), EORTC QLQ C30

    Time frame: 3 years after inclusion

    Description of the changes in HR-QoL scores from baseline to follow-up visits, measured by validated questionnaires using EORTC Quality of Life Questionnaire-core 30 (EORTC QLQ C30). The EORTC QLQ C30 is scored on 4 point Likert-scales: "Not at all", "A little", "Quite a bit", and "Very much."

  2. Evaluation of health-related quality of life (HRQoL), FACT-M

    Time frame: 3 years after inclusion

    Description of the changes in HR-QoL scores from baseline to follow-up visits, measured by validated questionnaires using Melanoma Surgery Specific subscale of the FACT-M. The FACT-M is scored on a 5 point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much."

  3. Description of the pathological response rates in the ILN

    Time frame: 1 year after inclusion

    The pathologic response rate is categorized into pathologic complete response (pCR), near-pCR, major pathologic response (MPR), pathologic partial response (pPR), pathologic no response (pNR), according to International Neoadjuvant Melanoma Consortium (INMC) criteria.

  4. Evaluation of the surgical morbidity, CTCAE v5

    Time frame: 2 year after inclusion

    Description of the incidence and severity of post-surgical complications according to CTCAE v5

  5. Evaluation of the surgical morbidity, Clavien Dindo

    Time frame: 2 year after inclusion

    Description of the incidence and severity of post-surgical complications according to Clavien Dindo

  6. Radiological evaluation of the index lymph node

    Time frame: 1 year after inclusion

    Calculate Concordance rates between radiological and pathological response (pCR, pPR, pNR) in the ILN

  7. Proportion of patients undergoing therapeutic lymph node dissection (TLND)

    Time frame: 5 years after inclusion

    Description of the proportion of patients undergoing TLND stratified by MPR and non-MPR status

  8. Melanoma specific survival

    Time frame: 5 years after inclusion

    Description of the Melanoma specific survival, as calculated time from the date of start of neoadjuvant therapy to the date of death due to melanoma

  9. Overall survival

    Time frame: 5 years after inclusion

    Description of the overall survival, as calculated time from the date of start of neoadjuvant therapy to the date of death due to melanoma or any cause

Study contacts

Contact information is provided by the study sponsor or research team.

Drik Grünhagen, MD, PhD

CONTACT

[email protected]

+31 10 704 19 02

Sponsors and collaborators

Lead sponsor

D.J. (Dirk) Grünhagen

Other

Registry information

Official study title

OMIT Trial: Omitting Therapeutic Lymph Node Dissection in Patients With Stage IIIB/C Melanoma and Major Pathological Response in the Index Lymph Node After Neoadjudvant Immunotherapy

Acronym: OMIT

Important dates

Study start
2025
Primary completion
2027
Study completion
2032
First posted
Jan 1, 2025
Registry last updated
Aug 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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