RecruitingPhase 3NCT07530887

NO Re-excision MelanomA - NORMA 2

Multicenter Phase 3 Randomized Controlled Trial of NO Re-excision MelanomA - NORMA 2


Sponsor

Marieke Goodijk

Enrollment

1,749 participants

Start Date

Nov 13, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This multicenter, phase III randomized controlled trial evaluates whether omitting re-excision after complete primary excision of cutaneous melanoma affects patient outcomes. A total of 1,749 patients with pT1b-pT4b cutaneous melanoma without evidence of metastases will be randomized to either standard re-excision according to current guidelines or no re-excision. Sentinel lymph node biopsy and adjuvant systemic therapy will be performed as indicated in both groups. The primary objective is to compare relapse-free survival (RFS) between the two groups. Secondary objectives include comparisons of overall survival (OS), local recurrence rates, recurrence of in-transit and lymph node metastases, distant metastasis-free survival (DMFS), surgical morbidity, quality of life, and health economic outcomes.


Eligibility

Inclusion Criteria13

  • Patients must be 18 years or older at time of consent
  • Patients must have an ECOG performance score between 0 and 2
  • Histologically confirmed, stage pT1b - pT4b (TNM AJCC 8th edition) cutaneous primary melanoma
  • Histological subtypes that are eligible are:
  • Superficial Spreading Melanoma (SSM)
  • Nodular Melanoma (NM)
  • The primary melanoma must have been removed by diagnostic excision and must have at least a minimum of 1 mm tumor free margin for invasive melanoma AND any in situ melanoma
  • Patient must provide informed consent and comply with the treatment protocol and follow-up plan
  • Life expectancy of at least 5 years from the time of diagnosis, not considering the melanoma in question, as determined by the investigator
  • A survivor of prior cancer is eligible provided that ALL of the following criteria are met and documented:
  • The patient has undergone potentially curative therapy for all prior malignancies
  • Life expectancy should be at least 5 years and
  • The patient is deemed by their treating physician to be at low risk of recurrence from previous malignancies.

Exclusion Criteria16

  • Non-cutaneous melanoma (uveal, mucosal)
  • Acral melanoma
  • Lentigo malignant melanoma (LMM)
  • Desmoplastic melanoma
  • Neurotropic melanoma
  • Spitz melanoma/malignant Spitz tumor melanoma
  • Satellites, in-transit melanomas or macroscopic melanoma metastases
  • Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesions of unknown malignant potential' (MELTUMP or STUMP)
  • Other non-SSM or NM subtypes
  • Melanoma removed by shave excision, excogliation or core biopsy
  • Patient has already undergone a local flap reconstruction of the defect after excision of the primary
  • History of previous or concurrent (i.e., second primary) invasive melanoma
  • Multiple melanomas
  • Patient has undergone surgery on a separate occasion to clear the lymph nodes of the probable draining lymphatic field, except for previous SLNB
  • Any additional solid tumor or hematologic malignancy during the past 5 years with a life expectancy of less than 5 years
  • History of organ transplantation

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Interventions

PROCEDURERe-excision

Prior to the re-excision, before any local anesthetic is given, the margin will be measured by a ruler and marked on the skin of the patient. The melanoma free margin of the diagnostic excision may be subtracted from the re-excision margin. The re-excision should be performed by cutting vertically down along the margins of the re-excision for its entire length until the required margin or until the fascia is reached in the depth. Removal of the fascia is left to the resecting surgeon's discretion. Preservation of anatomical structures, such as veins or nerves is allowed, if they are not clearly involved with tumor. In case of melanoma ≥pT3a any margin between 1 and 2 centimeter is accepted according to the surgeons preference. The amount of margin (in mm) taken during the re-excision needs to be documented perioperatively by the surgeon in the operation report. The specimen should be marked for anatomical navigation and sent off for pathological assessment.

PROCEDURENo re-excision

In case a patient is randomized toward the no-re-excision treatment arm, there is no need to perform any procedures to the primary tumor site.


Locations(21)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Flevoziekenhuis

Almere Stad, Netherlands

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Gelre ziekenhuizen

Apeldoorn, Netherlands

Rijnstate Ziekenhuis

Arnhem, Netherlands

Catharina ziekenhuis

Eindhoven, Netherlands

Medisch Spectrum Twente

Enschede, Netherlands

Groene Hart Ziekenhuis

Gouda, Netherlands

Martini ziekenhuis

Groningen, Netherlands

Tergooi MC

Hilversum, Netherlands

Dijklander Ziekenhuis

Hoorn, Netherlands

Alrijne Ziekenhuis

Leiden, Netherlands

Leids Universitair Medisch Centrum

Leiden, Netherlands

Maastricht UMC

Maastricht, Netherlands

Maasstad Ziekenhuis

Rotterdam, Netherlands

Haaglanden Medisch Centrum

The Hague, Netherlands

Haga Ziekenhuis

The Hague, Netherlands

Diakonessenhuis

Utrecht, Netherlands

St. Antonius Ziekenhuis

Utrecht, Netherlands

Isala Ziekenhuis

Zwolle, Netherlands

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