Excision of Lymph Node Trial (EXCILYNT) (Mel69)

Inclusion Criteria:

1. Provision of signed and dated informed consent form.

2. Stated willingness to comply with all study procedures and availability for theduration of the study.

3. Male or female, aged 18 years or older at enrollment

4. ECOG performance status of 0-2

5. Subjects must have histologically (or cytologically) confirmed metastatic melanomato only one lymph node in the axilla, groin, or iliac basin that was detectedclinically. A clinically positive lymph node is defined as a palpable and clinicallysuspicious node (based on palpation or imaging), or non-palpable lymph node that isFDG-avid or ≥ 0.95 cm on PET-CT, based on professional assessment of theradiologist, and that also is confirmed to contain metastatic melanoma on biopsy. a) The clinically positive lymph node may have been removed within 8 weeks prior toenrollment, and in that case may or may not have been evaluated by PET-CT; it isconsidered a clinically positive node if it was either identified as clinicallysuspicious on exam and/or on preoperative scans based on FDG-avidity and/or diameter ≥ 0.95 cm, and also confirmed histologically. The clinically positive node must bewithin the primary draining node basin of the primary melanoma, or the metastasismay be from an unknown primary site. A node that was removed at sentinel node biopsywill not meet this eligibility criterion. A patient will not be eligible if there isevidence of an additional clinically positive node on imaging or physical exam afterexcision of the first clinically positive node.

6. Subjects must be able to undergo LNEx and must not be on a clinical trial thatrequires TLND. a. Subjects may have previously had metastatic melanoma to a sentinel node in thesame node basin, if complete lymph node dissection was not done, and if at least 1year has elapsed since the prior positive sentinel node biopsy.

7. Individuals will be required to have radiological studies to rule out radiologicallyevident melanoma metastasis. Required studies include:

• PET-CT scan, and

• Head CT scan or MRI These scans may have been performed prior to resection ofthe primary melanoma and/or sentinel node biopsy if they showed no evidence ofother metastases.

Exclusion Criteria:

1. Subjects who have had a prior complete lymph node dissection or radiation therapy ofthe clinically positive node basin.

2. Subjects who have, or have had, in-transit or satellite metastases from the sameprimary melanoma that has metastasized to the cLN that is the focus of the currentstudy. a. The only exception are subjects who have had in-transit or satellite metastaseswithout intervening recurrence within the year prior to the subject's enrollment onthe study.

3. Subjects who have, or have had, one or more metastases distant to the primarydraining lymph node basin. An individual with small radiologic or clinical findingsof an indeterminate nature may still be eligible: examples include a new 5 mm lungnodule that is too small to characterize or an asymptomatic 12 mm bony lucency thatis not classic for malignancy, where clinical care may otherwise be to follow thepatient with repeat imaging rather than to treat the lesion.

4. Subjects with pre-existing lymphedema that precludes assessment of lymphedema.Pre-existing lymphedema should be discussed with the principal investigator (PI) atthe treating institution or the overall study PI. Some patients with mild stablelymphedema at the time of enrollment may still be evaluable. The primary endpointfor lymphedema measurement is the circumference 10 cm proximal to ankle/wrist on theinvolved side vs the contralateral side. If there is a pre-existing difference, thenit will be important to be able to assess for meaningful increases after surgery.

5. Subjects whose treating physician(s) plan adjuvant radiation therapy to the involvednode basin, because that also would confound assessment of node basin recurrence andlymphedema.

6. Individuals for whom there is a medical contraindication or potential problem incomplying with the requirements of the protocol in the opinion of the investigator.

7. Subjects with a prior or concurrent malignancy may be eligible if its naturalhistory or treatment does not have the potential to interfere with the safety orefficacy assessment of the regimen.

8. Subjects who are receiving systemic or intratumoral therapy for this melanoma within 3 months of enrollment. They may have received prior adjuvant systemic therapy foran earlier stage of disease, but should be off that therapy for 3 months prior toenrollment.

9. The only exception is for patients who are being treated at a participatingcenter with neoadjuvant therapy for 1 cLN, and who otherwise meet criteria forenrollment. They should be screened and enrolled as soon as possible. Theintent of this exception is to allow enrollment of patients who are beingevaluated at that center before the study is open but whose LN Excision datecan occur after the study is open to enrollment, or for patients who are notable to make a decision about enrollment on this study prior to startingneoadjuvant therapy. For such patients, data collected prior to startingneoadjuvant therapy should be recorded as screening data (such as imagingstudies), but baseline lymphedema measurements, FACT-M and WPAI surveys, andanything else not done prior to starting neoadjuvant therapy should beperformed as soon as possible, and prior to LN Excision. This exception doesreduce the power to address some exploratory endpoints; so, use of thisexception should be minimized as much as possible.