Complete Lymph Node Dissection or Observation in Treating Patients With Localized Melanoma and Sentinel Node Metastasis Who Have Undergone Sentinel Lymphadenectomy

Titre officiel

Multicentre Selective Lymphadenectomy Trial II (MSLT-II): A Phase III Multicentre Randomized Trial of Sentinel Lymphadenectomy and Complete Lymph Node Dissection Versus Sentinel Lymphadenectomy Alone in Cutaneous Melanoma Patients With Molecular or Histopathological Evidence of Metastases in the Sentinel Node

Sommaire:

JUSTIFICATION : L’évidemment ganglionnaire peut permettre de retirer les cellules tumorales qui se sont propagées aux ganglions lymphatiques avoisinants chez les patients atteints d’un mélanome malin localisé. Il peut arriver que, après la chirurgie, le traitement de la tumeur ne soit pas nécessaire avant que celle-ci ne progresse. Dans ce cas, la surveillance peut s’avérer suffisante. On ignore encore si l’évidemment ganglionnaire complet est plus efficace que l’observation pour traiter les patients atteints d’un mélanome malin localisé qui ont subi une lymphadénectomie sentinelle. BUT : Cet essai randomisé de phase III a pour but de comparer l’efficacité de l’évidemment ganglionnaire complet à celle de l’observation dans le traitement des patients atteints d’un mélanome malin localisé et de métastases au niveau du ganglion sentinelle qui ont subi une lymphadénectomie sentinelle.

Description de l'essai

Primary Outcome:

• Melanoma-specific survival

Secondary Outcome:

• Disease-free survival
• Time to recurrence (the first recurrence, any type)
• Time to regional lymph node recurrence
• Time to distant recurrence
• Time to recurrence in the regional lymph node basin
• Time to death from all causes
• Tumour burden in sentinel node, in terms of tumour area, tumour diameter, and interdigitating dendritic cells
• DNA/RNA markers in primary tumour, lymph node, and serum
• Genetic markers
• Serum tumour markers (e.g., TA90-IC, MIA, S-100)
• Quality of life assessed at baseline, at 4 and 12 months, and then annually for up to 10 years
• Surgery-related morbidity
• Adverse events
• Abnormal laboratory tests

OBJECTIVES:
Primary

• Compare the melanoma-specific survival of patients with localized cutaneous melanoma and sentinel node (SN) metastasis who undergo complete lymph node dissection (CLND) vs observation with serial nodal ultrasound after intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL).

Secondary

• Compare disease-free survival of these patients.
• Compare the frequency of same-basin recurrence after LM/SL in patients who do not undergo CLND with the frequency of nonsentinel node (NSN) metastasis detectable using histopathology specimens from patients who undergo CLND.
• Determine, prospectively, the prognostic accuracy of molecular staging by reverse transcriptase-polymerase chain reaction of the SN.
• Determine if new histopathologic techniques applied to SNs predict the presence of metastasis in the NSN and the likelihood of recurrence and death from melanoma.
• Determine if indices of the endogenous immune response to melanoma-associated antigens can predict regional or distant subclinical metastasis of melanoma before and after LM/SL.
• Assess patient blood samples before and after surgery for molecular markers (e.g., DNA, RNA, and proteomic markers [serum protein]) of melanoma.
• Assess patient blood samples before and after surgery for molecular tumour markers (e.g., MIA, S-100, TA90-IC) and evaluate their prognostic significance.
• Assess primary tumours of patients for DNA markers and evaluate the capacity of these markers to predict disease outcome.
• Retrospectively assess lymph nodes after CLND for evaluation of histopathologically inapparent occult metastases by molecular analysis.
• Compare the quality of life of these patients.

OUTLINE:

This is a prospective, randomized, multicentre study. Patients are stratified according to sentinel node status (positive by hematoxylin and eosin [H&E] staining or immunohistochemistry [IHC] vs negative by H&E or IHC but positive by reverse transcriptase-polymerase chain reaction [RT-PCR]), Breslow thickness (> 3.5 mm vs ≤ 3.5 mm), and participating center (MSLT centre vs non-MSLT centre). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo complete lymph node dissection (CLND) of the axillary, inguinal, popliteal, neck, or ectopic (if appropriate) lymph nodes.
• Arm II: Patients undergo observation comprising nodal ultrasound of the dissected nodal basin every 4 months for 2 years and then every 6 months for 3 years. Patients with nodes suspicious for recurrence undergo confirmatory biopsy of the nodal basin. If the nodal basin is tumour-positive, patients undergo CLND. Quality of life is assessed at baseline, at 4 and 12 months, and then annually for up to 10 years. After completion of study treatment, patients are followed periodically for up to 10 years.

Voir cet essai sur ClinicalTrials.gov