Multicenter Selective Lymphadenectomy Trial II (MSLT-II)

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Procedure: Monitoring with nodal ultrasound; Procedure: Completion Lymphadenectomy

• Study Type: Interventional
• Enrollment (Actual): 1939
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2298
      • Newcastle Melanoma Unit
    • Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • East Hawthorn, Victoria, Australia, 3123
      • Alfred Hospital
    • East Melbourne, Victoria, Australia, 3677
      • Peter Maccallum Cancer Centre
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Tom Baker Cancer Center
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Sunnybrook Health Sciences Center
• Finland
  • Helsinki, Finland, 00029 HUS
    • Helsinki Unversity Hospital
• Germany
  • Lubeck, Germany, 23538
    • U. Hosp. Schleswig-Holstein/Campus Lubeck
  • Nurnberg, Germany, 90419
    • City Hospital of Nurnberg
  • Wurzburg, Germany, 97080
    • University of Würzburg
• Israel
  • Tel-Aviv, Israel, 94239
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Milan, Italy, 20141
    • Istituto Europeo Di Oncologia
  • Naples, Italy, 80121
    • Istituto Nazionale dei Tumori Napoli
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto - University of Padova
  • Padua, Italy, 35128
    • Padua University - Clinica Chirurgica II
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute
  • Groningen, Netherlands, 9700 RB
    • Universitair Medisch Centrum Groningen
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
• Sweden
  • Lund, Sweden, S-221 85
    • Swedish Melanoma Study Group
• Switzerland
  • Lausanne, Switzerland, CH 1011
    • Centre Hospitalier Universitaire Vaudois
  • Zurich, Switzerland, CH-8091
    • University of Zurich
• United Kingdom
  • London, United Kingdom, SE17EH
    • Saint Thomas's Hospital
  • Norwich
    • Norfolk, Norwich, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospital
• United States
  • California
    • San Diego, California, United States, 92123
      • Sharp Hospital
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 809030-3658
      • Memorial Hospital - Colorado Springs
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60612-3824
      • Rush University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medical Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0932
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110-8566
      • St. Louis University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14209
      • Buffalo General Hospital
    • Great Neck, New York, United States, 11021
      • Feinstein Institute for Medical Research
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Stony Brook, New York, United States, 11794-8191
      • SUNY at Stony Brook Hospital Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Clinic
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State Hershey Cancer Institute
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Wynnewood, Pennsylvania, United States, 19096
      • Main Line Surgeons
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37232-6868
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75235
      • Dallas Surgical Group
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • IHC Cancer Services Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84112
      • Hunstman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Newport News, Virginia, United States, 23606
      • Sentara Careplex Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ultrasound observation + delayed CLND if recurrence detected	Procedure: Monitoring with nodal ultrasound; serial ultrasound monitoring of SLND positive basin. If recurrence detected, subject has CLND.
Active Comparator: CLND	Procedure: Completion Lymphadenectomy; complete lymph node dissection of lymph node basin with positive node

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival over 10 years of follow up	10 years
Recurrence during 10 years of follow up	10 years

Collaborators and Investigators

• Sponsor: Saint John's Cancer Institute
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Richard Essner, M.D., Saint John's Cancer Institute

Publications and helpful links

General Publications

• 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. Erratum In: JAMA Surg. 2022 Sep 1;157(9):859.
• 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.

Helpful Links

• John Wayne Cancer Institute Clinical Trials (sponsor)

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2004
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: February 27, 2006
• First Submitted That Met QC Criteria: February 28, 2006
• First Posted (Estimate): March 1, 2006

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: surgical; sentinel lymph node dissection; complete lymph node dissection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: MSLT-II; P01CA029605 (U.S. NIH Grant/Contract); R01CA189163 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No