Clinical trial NCT00297895: Multicenter Selective Lymphadenectomy Trial II (MSLT-II)
Official title: A Phase III Multicenter 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma
Keywords: sentinel lymph node dissection
complete lymph node dissection
surgical
Lead sponsor: Saint John's Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2006-03-01
Enrollment: 1939
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Subjects must be diagnosed with melanoma. All subjects receive sentinel lymphadenectomy. If the subject is sentinel node positive and meets study requirements, the subject is randomized to receive either (1) completion lymphadenectomy (2) observation with nodal ultrasound. Subjects are then followed for 10 years.


Eligibility criteria: Inclusion Criteria:

1. Ability to provide informed consent.
2. Between 18 and 75 years of age.
3. Have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm, sole, subungual skin tissues).
4. Have clear margins following WLE.
5. ECOG performance status 0-1.
6. Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI.
7. Willing to return to the MSLT-II center for follow up examinations and procedures as outlined in the protocol.
8. Randomization and/or CLND (as appropriate to randomization arm) must be completed no more than 120 days following the diagnostic biopsy of the primary melanoma.
9. Have a melanoma-related tumor-positive SN, determined by either of the following methods:

   1. Diagnosis of tumor-positive SN by MSLT-II center institutional pathologist by either H\&E or IHC (using S-100, Mart-1, and HMB-45).
   2. Diagnosis of tumor-positive SN by RT-PCR analysis performed at JWCI, provided the primary melanoma fits into one of the following categories:

      * Breslow thickness of 1.20 mm or greater and Clark Level III
      * Clark Level IV or V, regardless of Breslow thickness
      * Ulceration, regardless of Breslow thickness or Clark level

Exclusion Criteria:

1. History of previous or concurrent (i.e., second primary) invasive melanoma.
2. Primary melanoma of the eye, ears, mucous membranes or internal viscera. (Primary of the skin of the external ear is acceptable.)
3. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic disease.
4. Any additional solid tumor or hematologic malignancy during the past 5 years except T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine cervical cancer.
5. Skin grafts, tissue transfers or flaps that have the potential to alter the lymphatic drainage pattern from the primary melanoma to a LN basin.
6. Allergy to vital blue dye or any radiocolloid.
7. Inability to localize 1-2 SN drainage basins via LM (e.g., no basins found, more than 2 basins found, proximity of the primary melanoma to the regional draining basin, etc.)
8. CLNDs or SLs (before evaluation of the current melanoma) that may have altered the lymphatic drainage pattern from the primary cutaneous melanoma to a potential LN basin.
9. Organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the full protocol, or be exacerbated by therapy (e.g., severe depression).
10. Melanoma-related operative procedures not corresponding to criteria described in the protocol.
11. Primary or secondary immune deficiencies or known significant autoimmune disease.
12. History of organ transplantation.
13. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at any time during study participation or within 6 months prior to enrollment.
14. Pregnant or lactating women.
15. Participation in concurrent therapy protocols of alternative local nodal basin therapies that might confound the analysis of this trial is not permitted. For example, radiation of a non-resected node basin is not acceptable because it might influence outgrowth of residual melanoma in that nodal basin. However, systemic adjuvant therapy or clinical trial adjuvant protocols after the finding of a positive node on LM/SL or delayed nodal recurrence in the ultrasound observation arm are both acceptable according to the standard of care at the multicenter site. Patients with positive sentinel nodes or thick primary melanomas who are considered by the multicenter site's investigator as high-risk may receive systemic adjuvant therapy according to the standard practice of that particular site.
16. SLND pathology shows, on microscopic examination, that melanoma extends through the lymph node capsule into the adjacent soft tissue.

Primary outcomes:
measure: Melanoma-specific survival. This is defined as the time between the date of a subject's randomization (or date of CLND for those randomized to the CLND arm) and the date of death due to melanoma. Subjects are followed until death or 10yrs.
timeFrame: 10 years
Secondary outcomes:
measure: Disease-free survival over 10 years of follow up
timeFrame: 10 years
measure: Recurrence during 10 years of follow up
timeFrame: 10 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Sharp Hospital
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Colorado Springs
country: United States
facility: Memorial Hospital - Colorado Springs
state: Colorado
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institute
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Great Neck
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: SUNY at Stony Brook Hospital Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Hershey
country: United States
facility: Pennsylvania State Hershey Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Surgeons
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Dallas Surgical Group
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: IHC Cancer Services Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Hunstman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Newport News
country: United States
facility: Sentara Careplex Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Newcastle
country: Australia
facility: Newcastle Melanoma Unit
state: New South Wales
city: Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: East Hawthorn
country: Australia
facility: Alfred Hospital
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Helsinki
country: Finland
facility: Helsinki Unversity Hospital
city: Lubeck
country: Germany
facility: U. Hosp. Schleswig-Holstein/Campus Lubeck
city: Nurnberg
country: Germany
facility: City Hospital of Nurnberg
city: Wurzburg
country: Germany
facility: University of Wurzburg
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Naples
country: Italy
facility: Istituto Nazionale dei Tumori Napoli
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - University of Padova
city: Padua
country: Italy
facility: Padua University - Clinica Chirurgica II
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Lund
country: Sweden
facility: Swedish Melanoma Study Group
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: University of Zurich
city: Norfolk
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norwich
city: London
country: United Kingdom
facility: Saint Thomas's Hospital
Study officials:
affiliation: Saint John's Cancer Institute
name: Richard Essner, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Multicenter Selective Lymphadenectomy Trials Study Group; Crystal JS, Thompson JF, Hyngstrom J, Caraco C, Zager JS, Jahkola T, Bowles TL, Pennacchioli E, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, van Akkooi A, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Neves RI, Rossi CR, Kane JM 3rd, Trocha S, Wright F, Byrd DR, Matter M, Hsueh EC, MacKenzie-Ross A, Kelley M, Terheyden P, Huston TL, Wayne JD, Neuman H, Smithers BM, Ariyan CE, Desai D, Gershenwald JE, Schneebaum S, Gesierich A, Jacobs LK, Lewis JM, McMasters KM, O'Donoghue C, van der Westhuizen A, Sardi A, Barth R, Barone R, McKinnon JG, Slingluff CL, Farma JM, Schultz E, Scheri RP, Vidal-Sicart S, Molina M, Testori AAE, Foshag LJ, Van Kreuningen L, Wang HJ, Sim MS, Scolyer RA, Elashoff DE, Cochran AJ, Faries MB. Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial. JAMA Surg. 2022 Sep 1;157(9):835-842. doi: 10.1001/jamasurg.2022.2055.
citation: Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, Jahkola T, Bowles TL, Testori A, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, Wouters MWJM, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Rossi CR, Neves RI, Trocha SD, Wright F, Byrd DR, Matter M, Hsueh E, MacKenzie-Ross A, Johnson DB, Terheyden P, Berger AC, Huston TL, Wayne JD, Smithers BM, Neuman HB, Schneebaum S, Gershenwald JE, Ariyan CE, Desai DC, Jacobs L, McMasters KM, Gesierich A, Hersey P, Bines SD, Kane JM, Barth RJ, McKinnon G, Farma JM, Schultz E, Vidal-Sicart S, Hoefer RA, Lewis JM, Scheri R, Kelley MC, Nieweg OE, Noyes RD, Hoon DSB, Wang HJ, Elashoff DA, Elashoff RM. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017 Jun 8;376(23):2211-2222. doi: 10.1056/NEJMoa1613210.