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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07049276




Registration number
NCT07049276
Ethics application status
Date submitted
24/05/2025
Date registered
3/07/2025
Date last updated
3/07/2025

Titles & IDs
Public title
The Multicentre Selective Lymphadenectomy Trial - 3
Scientific title
Randomized Controlled Trial of Selective Index Lymph Node Resection Versus Therapeutic Lymph Node Dissection After Neoadjuvant Immunotherapy for Stage IIIB-D Melanoma
Secondary ID [1] 0 0
MIA2024/501
Universal Trial Number (UTN)
Trial acronym
MSLT-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Melanoma, Stage III 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Index lymph node resection
Treatment: Surgery - Therapeutic lymph node dissection

Experimental: Index Lymph Node - The largest affected (index) lymph node marked with a clip under ultrasound or X-ray guidance and then removed after neoadjuvant therapy for the pathological response to be determined. The response then dictates the next step of management

Active comparator: Therapeutic lymph node dissection - Complete removal of all nodes in the regional lymph node basin


Treatment: Surgery: Index lymph node resection
The largest lymph node affected with melanoma

Treatment: Surgery: Therapeutic lymph node dissection
Removal of all nodes in the melanoma affected lymph node basin
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence free survival
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
The rate of escalation to a therapeutic lymph node dissection (TLND) in the ILN arm due to isolated nodal recurrence in the ILN nodal basin
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
The salvage rate with surgery, radiotherapy or new systemic therapy post operatively for disease recurrence in each surgical arm with a major pathological response (complete pathological response or near complete pathological response)
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Distant metastasis free-survival
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
10 years
Secondary outcome [5] 0 0
Surgery-related adverse events
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Surgery-related adverse events
Timepoint [6] 0 0
6 to 12 weeks
Secondary outcome [7] 0 0
Patient-rated quality of life QLQ C30
Timepoint [7] 0 0
6, 12, 24, 36 and 48 weeks
Secondary outcome [8] 0 0
Patient-rated quality of life EQ 5D5L
Timepoint [8] 0 0
6, 12, 24, 36 and 48 weeks
Secondary outcome [9] 0 0
Patient-rated quality of life FACT-M
Timepoint [9] 0 0
6, 12, 24, 36 and 48 weeks
Secondary outcome [10] 0 0
Concordance of metabolic response with pathological response
Timepoint [10] 0 0
week 6
Secondary outcome [11] 0 0
Concordance of metabiolic response with RECIST response
Timepoint [11] 0 0
week 6
Secondary outcome [12] 0 0
Concordance of metabolic response with circulating ctDNA
Timepoint [12] 0 0
week 6
Secondary outcome [13] 0 0
Health-related economic costs
Timepoint [13] 0 0
2 years

Eligibility
Key inclusion criteria
1. Male or female patients = 18 years of age at the time of consent
2. Written informed consent
3. Cytologically or histologically confirmed, resectable pathological Stage IIIB, C or D (Any T, N1b, N2b, N2c, N3b, or N3c) cutaneous or unknown primary melanoma, with or without primary tumour in situ
4. A minimum of one macroscopic lymph node, defined as:

* A palpable node, confirmed by pathology
* A non-palpable node, but enlarged per RECIST 1.1 criteria (= 15 mm in shortest diameter) and confirmed by pathology
* An ultrasound or PET/CT scan positive lymph node of any size, confirmed by pathology.
5. Up to 3 satellite (defined as any foci of clinically evident cutaneous and/or subcutaneous metastases occurring within 2 cm of but discontinuous from the primary melanoma) or in-transit metastases (defined as clinically evident cutaneous and/or subcutaneous metastases occurring >2 cm from the primary melanoma in the region between the primary and the regional lymph node basin) are permitted if they are completely resectable.
6. Lymph node involvement in the groin (iliac, inguinal or both), axilla or neck only and may be unilateral or bilateral. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
7. Tumour amenable to a newly obtained core biopsy of a lesion which has not been previously irradiated. Archival tissue from a past primary or nodal lesion (if applicable) or tissue taken for current diagnosis will also be collected if available.
8. Systemic neoadjuvant immunotherapy is scheduled for administration with at least one PD-(L)-1 check point inhibitor (e.g. nivolumab, pembrolizumab, cemiplimab). The immunotherapy regimen may include other checkpoint inhibitors (e.g. ipilimumab, relatlimab, fianlimab). The patient should meet the fitness for treatment requirements as detailed in the relevant regulatory-approved Product Information or Summary of Product Characteristics.
9. Neoadjuvant course of treatment to be no longer than 6 weeks (allows for a maximum of 3 cycles at weeks 0, 3 and 6).
10. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
11. Anticipated life expectancy of > 5 years.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Uveal or mucosal melanoma.
2. Isolated satellite or in-transit metastases only (without any cytological or histological proven lymph node involvement).
3. Involvement of any lymph node basin other than groin, axilla or neck. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
4. Clinical or radiographic evidence of distant metastasis (any AJCC 8th ed M Stage).
5. Previous history of lymph node surgery to the same nodal basin, that was more extensive than a sentinel lymph node biopsy (SLNB).
6. Previous radiotherapy to the same nodal basin.
7. Any contraindication to the administration of nivolumab, ipilimumab, pembrolizumab or relatlimab per regulatory-approved product information and / or medical oncologist.
8. Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment.
9. A plan to administer targeted therapy or any non-checkpoint inhibitor immunotherapy, or any intralesional therapy for melanoma in the neoadjuvant setting.
10. A plan to administer any experimental immunotherapy as part of a clinical trial in the neoadjuvant setting.
11. Known additional malignancies (unless adequately treated) active within the previous 3 years, except for locally curable cancers that have been apparently cured. The following malignancies, if undergone successful definitive resection or curative treatment, are permitted:

* Basal cell carcinoma of the skin
* Squamous cell carcinoma of the skin
* Carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, but excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy
* Prostatic intraepithelial neoplasia
* In situ melanoma
* Atypical melanocytic hyperplasia
* Stage I melanoma
* Other malignancies for which the patient has been disease free for 3 years, not requiring active anti-cancer therapy.
12. An active autoimmune disease or a requirement for chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. The following are permitted:

* Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient is on a stable dose
* Non-absorbed intra-articular steroid injections.
13. Has had an allogenic tissue/solid organ transplant.
14. Active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
15. Has a known history of Human Immunodeficiency Virus (HIV). Note: no testing for HIV is required unless mandated by local health authority.
16. Pregnant or breastfeeding females.
17. Concurrent medical or social conditions that may prevent the patient from attending assessments or procedures per schedule.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2040
Actual
Sample size
Target
1500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Italy
State/province [3] 0 0
Perugia
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auklnad
Country [5] 0 0
United Kingdom
State/province [5] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alexander CJ van Akkooi
Address 0 0
Melanoma Institute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alexander CJ van Akkooi
Address 0 0
Country 0 0
Phone 0 0
+612 9911 7200
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT07049276