Omitting re-excision after complete primary melanoma excision

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

This trial tests whether people with pT1b–pT4b cutaneous melanoma whose tumors were completely removed can safely skip the usual re-excision surgery.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1749 (estimated)
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Locations: 21 sites ('s-Hertogenbosch and 20 other locations)
• Trial ID: NCT07530887 on ClinicalTrials.gov

What this trial studies

This is a multicenter, phase III randomized non-inferiority trial that will enroll 1,749 patients with pT1b–pT4b cutaneous melanoma and no evidence of metastasis. Participants are randomized 1:1 to standard re-excision according to local guidelines or to omission of re-excision, with sentinel lymph node biopsy and adjuvant therapy performed as indicated in both groups. The primary endpoint is relapse-free survival, with secondary endpoints including overall survival, local and regional recurrence patterns, surgical morbidity, quality of life, and health economic outcomes. Patients will be followed for up to five years to capture recurrence and survival events.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed pT1b–pT4b primary cutaneous melanoma who had a complete diagnostic excision with tumor-free margins, ECOG 0–2, and no evidence of regional or distant metastases are ideal candidates.

Not a fit: Patients with positive surgical margins, known regional or distant metastases, tumor subtypes not included in the protocol, or those unable to attend follow-up at participating centers are unlikely to benefit from omission of re-excision.

Why it matters

Potential benefit: If successful, the approach could allow many patients to avoid an extra surgery, reducing surgical morbidity, improving quality of life, and lowering healthcare costs.

How similar studies have performed: Some retrospective and observational reports have suggested selected patients may safely avoid wider re-excision, but there is no large phase III randomized evidence yet.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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

Where this trial is running

's-Hertogenbosch and 20 other locations

• Jeroen Bosch Ziekenhuis — 's-Hertogenbosch, Netherlands (Recruiting)
• Noordwest Ziekenhuisgroep — Alkmaar, Netherlands (Recruiting)
• Flevoziekenhuis — Almere Stad, Netherlands (Recruiting)
• Antoni van Leeuwenhoek — Amsterdam, Netherlands (Recruiting)
• Gelre ziekenhuizen — Apeldoorn, Netherlands (Recruiting)
• Rijnstate Ziekenhuis — Arnhem, Netherlands (Recruiting)
• Catharina ziekenhuis — Eindhoven, Netherlands (Not_yet_recruiting)
• Medisch Spectrum Twente — Enschede, Netherlands (Recruiting)
• Groene Hart Ziekenhuis — Gouda, Netherlands (Not_yet_recruiting)
• Martini ziekenhuis — Groningen, Netherlands (Not_yet_recruiting)
• Tergooi MC — Hilversum, Netherlands (Not_yet_recruiting)
• Dijklander Ziekenhuis — Hoorn, Netherlands (Not_yet_recruiting)
• Alrijne Ziekenhuis — Leiden, Netherlands (Not_yet_recruiting)
• Leids Universitair Medisch Centrum — Leiden, Netherlands (Recruiting)
• Maastricht UMC — Maastricht, Netherlands (Not_yet_recruiting)
• Maasstad Ziekenhuis — Rotterdam, Netherlands (Not_yet_recruiting)
• Haaglanden Medisch Centrum — The Hague, Netherlands (Recruiting)
• Haga Ziekenhuis — The Hague, Netherlands (Not_yet_recruiting)
• Diakonessenhuis — Utrecht, Netherlands (Recruiting)
• St. Antonius Ziekenhuis — Utrecht, Netherlands (Not_yet_recruiting)
• Isala Ziekenhuis — Zwolle, Netherlands (Not_yet_recruiting)

Study contacts

• Study coordinator: Y. (Yvonne) M. Schrage, MD PhD

Conditions Melanoma; primary cutaneous melanoma; re-excision; de-escalation