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 nivolumab in combination with ipilimumab.
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
- Skin and subcutaneous tissue therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The two coprimary endpoints are 2-year LRFS and 2-year DMFS
Secondary outcome
• To evaluate the HR-QoL from baseline to follow-up visits.
• To describe the rates of pathological complete response (pCR), near-pCR,
pathologic partial response (pPR), and pathologic non-response (pNR) in the ILN.
• To describe surgical morbidity
• To describe Concordance between radiological response and pathological
response (pCR, pPR, pNR) in the ILN.
• To describe the proportion of patients (eventually) undergoing TLND
stratified by MPR and non-MPR status.
• To describe melanoma specific survival and overall survival.
• To describe surgical adverse events (AEs) and neoadjuvant immunotherapy AEs
Background summary
Two randomized trials, NADINA and SWOG-1801, have demonstrated that neoadjuvant
treatment with anti-PD1 improves event-free survival in patients with
macroscopic resectable stage III melanoma. In these studies, 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 DMFS). The PRADO trial indicated that the MPR
definition can also be revealed from an surrogate lymph node response, the
index lymph node (ILN), allowing sparing the extensive surgery in MPR
patients. In these MPR patients the distant metastasis free survival (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 a MPR within the ILN after
neoadjuvant immunotherapy.
Study objective
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 nivolumab in combination with ipilimumab.
Study design
This study is a prospective, single-arm phase 2 nationwide multicenter trial
Intervention
Performing an Index node (ILN) procedure and if patients achieve a MPR in the
index node, the TLND will be omitted
Study burden and risks
Participants will be treated according to standard of care neoadjuvant
immunotherapy and lymph node dissection after marking the largest LN
metastasis, the and ILN. The study inherent burden includes additional
follow-up visits, blood draws, and imaging as compared to SoC. An additional
burden is the double surgery intervention for non-MPR patients (ILN followed by
TLND), while patients achieving an MPR might benefit from the less extensive
surgery burden as compared to SoC (TLND) as as shown in PRADO to improve their
QoL. Another risk is a potential increase in local recurrence when omitting the
TLND in MPR patients, although current data suggest that this risk is small (7%
at 2 years) in patients who achieve a MPR. Additionally, if local recurrence
does occur, a TLND can still be performed, resulting in a DMFS of 98% at 2
yearsfor MPR patients.
Potential benefits from participating in this trial would be avoiding an
extensive and potentially morbid surgery (TLND) in MPR patients, without
increase of DMFS, but potentially significantly improved quality of life
dr. Molewaterplein 40
Rotterdam 3015GD
NL
dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
• Patients must be eligible for neoadjuvant treatment
• 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:
o a palpable node, confirmed as melanoma by pathology;
o a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15
mm in short axis), confirmed as melanoma by pathology;
o 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
• in-transit metastases only (without cytological or histological proven lymph
node involvement)
• Melanoma located in the head and neck region, where performing two surgeries
is deemed to result in significant morbidity
• Patients with (history of) distant metastasis (stage IV melanoma).
• Presence of more than 3 in-transit metastases
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT06754904 |
| CCMO | NL88017.078.24 |