NO Re-excision MelanomA - NORMA 2
NORMA-2
Multicenter Phase 3 Randomized Controlled Trial of NO Re-excision MelanomA - NORMA 2
2 other identifiers
interventional
1,749
1 country
21
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2025
Longer than P75 for phase_3
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 13, 2025
CompletedFirst Submitted
Initial submission to the registry
March 26, 2026
CompletedFirst Posted
Study publicly available on registry
April 15, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2033
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2033
April 15, 2026
April 1, 2026
8 years
March 26, 2026
April 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Relapse-Free Survival (RFS)
RFS, defined as time from randomization to any first melanoma recurrence or melanoma-related death, whichever occurs first. Any new primary melanoma and/or melanoma in situ will be registered. However, it will not be considered an event for the primary endpoint of RFS.
From randomization to the first occurrence of melanoma recurrence or melanoma-related death, assessed up to 5 years.
Secondary Outcomes (13)
Overall Survival (OS)
From randomization to death from any cause, assessed up to 5 years.
Local Recurrence Rate (LRR)
From randomization up to 5 years
Recurrence rate of in-transit metastases
From randomization up to 5 years
Recurrence rate of lymph node metastases
From randomization up to 5 years
Distant Metastasis-Free Survival (DMFS)
From randomization to the first occurrence of distant metastasis, assessed up to 5 years
- +8 more secondary outcomes
Study Arms (2)
Arm A (control): re-excision
ACTIVE COMPARATORRe-excision (according to local protocol between 1 and 2 cm margins)
Arm B (experimental): no re-excision
EXPERIMENTALNo re-excision
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Marieke Goodijklead
- Dutch Cancer Societycollaborator
Study Sites (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
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- M.T. Goodijk, MD, PhD Candidate Surgical Oncology
Study Record Dates
First Submitted
March 26, 2026
First Posted
April 15, 2026
Study Start
November 13, 2025
Primary Completion (Estimated)
November 1, 2033
Study Completion (Estimated)
November 1, 2033
Last Updated
April 15, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share