Multicenter Selective Lymphadenectomy Trial II (MSLT-II)

• ClinicalTrials.gov Identifier: NCT00297895
• Recruitment Status: Completed
• First Posted: March 1, 2006
• Last Update Posted: May 13, 2022
• Sponsor: Saint John's Cancer Institute
• Collaborators: National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): Saint John's Cancer Institute

Tracking Information

• First Submitted Date: February 27, 2006
• First Posted Date: March 1, 2006
• Last Update Posted Date: May 13, 2022
• Actual Study Start Date: September 30, 2004
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 30, 2009): 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. [ Time Frame: 10 years ]
• Original Primary Outcome Measures (submitted: February 28, 2006): 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.

Current Secondary Outcome Measures (submitted: April 30, 2009)

• Disease-free survival over 10 years of follow up [ Time Frame: 10 years ]
• Recurrence during 10 years of follow up [ Time Frame: 10 years ]

Original Secondary Outcome Measures (submitted: February 28, 2006)

• Disease-free survival over 10 years of follow up
• Recurrence during 10 years of follow up

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Procedure: Completion Lymphadenectomy
  complete lymph node dissection of lymph node basin with positive node
• Procedure: Monitoring with nodal ultrasound
  serial ultrasound monitoring of SLND positive basin. If recurrence detected, subject has CLND.

Study Arms

• Active Comparator: Ultrasound observation + delayed CLND if recurrence detected
  Intervention: Procedure: Monitoring with nodal ultrasound
• Active Comparator: CLND
  Intervention: Procedure: Completion Lymphadenectomy

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 30, 2019): 1939
• Original Enrollment (submitted: February 28, 2006): 1925
• Actual Study Completion Date: September 30, 2019
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Finland, Germany, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
• Removed Location Countries: Ireland

Administrative Information

• NCT Number: NCT00297895
• Other Study ID Numbers: MSLT-II; P01CA029605 ( U.S. NIH Grant/Contract ); R01CA189163 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Saint John's Cancer Institute
• Original Responsible Party: Not Provided
• Current Study Sponsor: Saint John's Cancer Institute
• Original Study Sponsor: Same as current

Collaborators

• National Institutes of Health (NIH)
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Richard Essner, M.D.; Saint John's Cancer Institute

• PRS Account: Saint John's Cancer Institute
• Verification Date: May 2022