Lymph Node Removal Timing for Melanoma

(EXCILYNT Trial)

Recruiting at 6 trial locations

Overseen By Samantha Schaeffer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Craig L Slingluff, Jr

Must not be taking: Systemic therapy

Disqualifiers: Prior lymph node dissection, Radiation therapy, Distant metastases, Pre-existing lymphedema, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

66 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if removing only the cancerous lymph node (known as a lymph node excision) is effective at preventing cancer from coming back in the same area of the lymph node excision. The study team is also trying to find out the side effects of this type of surgery and how much the surgery impacts quality of life. In order to be eligible for this study, participants must have been diagnosed with metastatic melanoma and have one detected cancerous lymph node by imaging (CT/PET scan) or clinical examination, and are a candidate for lymph node excision.

Will I have to stop taking my current medications?

The trial requires that participants stop any systemic or intratumoral therapy for melanoma at least 3 months before enrolling. If you are on such treatments, you will need to stop them to participate.

What data supports the effectiveness of this treatment for melanoma?

Research shows that removing lymph nodes after neoadjuvant systemic therapy (treatment given before the main treatment) for stage III melanoma does not lead to worse surgical outcomes compared to removing them upfront. Additionally, early intervention with sentinel lymph node biopsy in certain patients can improve long-term survival. ^{1 2 3 4 5}

Is lymph node removal generally safe for melanoma patients?

Lymph node removal, including procedures like sentinel lymph node biopsy and lymph node dissection, is generally considered safe, but it can have complications. Studies have shown that while these procedures can help in managing melanoma, they may come with risks such as postoperative complications and morbidity (health problems after surgery). ^{1 3 4 6 7}

How does the timing of lymph node removal for melanoma differ from other treatments?

This treatment is unique because it involves removing lymph nodes either before or after systemic therapy, depending on when metastasis is detected. Unlike traditional approaches that often involve immediate lymph node removal, this method allows for flexibility based on the patient's response to initial systemic therapy, potentially reducing unnecessary surgery and its complications. ^{1 2 8 9 10}

Research Team

Craig L. Slingluff, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for adults with melanoma that has spread to only one lymph node, which can be removed by surgery. They must have good performance status (able to carry out daily activities), no prior complete lymph node dissection or radiation in the affected area, and no other cancer treatments within 3 months before joining.

Inclusion Criteria

I can have a lymph node exam and am not in a trial needing total lymph node removal.

I had a suspicious lymph node removed recently, which may not have been checked with a PET-CT.

I had melanoma spread to a lymph node but didn't have all nodes removed, and it's been over a year.

Exclusion Criteria

My doctor plans to give me radiation therapy after surgery to the area where my cancer was.

I already have lymphedema that cannot be further assessed.

I have had all lymph nodes removed or radiation on the affected area.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Excision of the clinically detected metastatic lymph node

1 day

1 visit (in-person)

Follow-up

Participants are monitored for recurrence of melanoma and side effects such as lymphedema

3 years

Treatment Details

Interventions

• Excision of clinically detected lymph node metastasis after neoadjuvant systemic therapy
• Excision of clinically detected lymph node metastasis before any systemic therapy

Trial Overview The study tests whether removing a single cancerous lymph node before or after neoadjuvant systemic therapy prevents cancer recurrence in the same area. It also examines the surgery's side effects and its impact on patients' quality of life.

Participant Groups

Group I: Cohort 2: Excision of cLN after neoadjuvant systemic therapy Experimental Treatment 1 Intervention

Excision of the clinically detected metastatic lymph node after systemic neoadjuvant therapy.

Group II: Cohort 1: Excision of cLN before systemic therapy Experimental Treatment 1 Intervention

Excision of the clinically detected metastatic lymph node before systemic therapy.

Excision of clinically detected lymph node metastasis after neoadjuvant systemic therapy is already approved in United States, European Union for the following indications:

Approved in United States as Lymph Node Excision for:

• Metastatic melanoma

Approved in European Union as Excision of Clinically Detected Lymph Node Metastasis for:

• Metastatic melanoma

Who Is Running the Clinical Trial?

Craig L Slingluff, Jr

Lead Sponsor

Trials

24

Recruited

750+

Findings from Research

Early diagnosis and total tumor excision are crucial for successful treatment of malignant melanoma, with recent studies suggesting that narrower excision margins (1-3 cm) can achieve similar survival rates as larger margins (up to 5 cm).

Sentinel lymph node biopsy is a valuable technique that helps identify the first lymph node likely to contain metastasis, allowing for targeted treatment and potentially reducing the need for extensive lymphadenectomy, which has high complication rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical treatment of malignant melanoma]. Bösch, U., Banic, A.[2012]

Surgery is the primary treatment for patients with localized melanoma (stages 0-II), involving wide excision and sentinel lymph node biopsy when necessary.

For stage III melanoma, surgery is preferred for patients with limited metastases, but the use of effective preoperative drugs should be considered, while stage IV melanoma management should involve a multidisciplinary team for optimal decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of melanoma. Sondak, VK., Gibney, GT.[2014]

The MSLT-I trial demonstrated that sentinel lymph node biopsy (SLNB) does not improve 10-year melanoma-specific survival compared to wide local excision (WLE) alone, as both groups had similar rates of nodal positivity (20.8%).

However, for patients with intermediate-thickness melanoma (1.2-3.5 mm Breslow depth) who had positive sentinel nodes, early intervention after SLNB significantly improved 10-year distant disease-free survival and melanoma-specific survival, indicating a potential benefit for this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in melanoma: final results of MSLT-I. Durham, AB., Wong, SL.[2018]

In a study of 120 patients with high-risk stage III melanoma, those who received neoadjuvant systemic therapy (anti-PD1 and anti-CTLA4) showed comparable surgical outcomes to those who underwent upfront surgery, with no significant differences in postoperative complications (31.8% vs. 36.8%) or morbidity rates.

The duration of surgery was slightly longer for the neoadjuvant group (105 minutes vs. 90 minutes), but this difference was not statistically significant, indicating that neoadjuvant therapy does not adversely affect surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical outcomes of lymph node dissections for stage III melanoma after neoadjuvant systemic therapy are not inferior to upfront surgery. Zijlker, LP., van der Burg, SJC., Blank, CU., et al.[2023]

The study compares the outcomes of two surgical approaches for treating cutaneous melanoma: wide excision with lymphadenectomy versus radical excision alone, using data from sentinel node biopsies.

The analysis focuses on both immediate and long-term results, highlighting the importance of lymphadenectomy in potentially improving patient outcomes after melanoma surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Significance of lymphadenectomy of "sentinel" lymph nodes in combined treatment of cutaneous melanoma localized on extremities and the trunk]. [2023]

Recent clinical trials have significantly changed melanoma management practices, particularly regarding the roles of sentinel node biopsy and adjuvant therapies, leading to updated guidelines from Cancer Council Australia.

For patients with Stage III melanoma, less invasive surgical options are now recommended, with a greater focus on life-prolonging systemic therapies, highlighting the importance of accurate tumor staging for effective treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of cutaneous melanoma. Mar, VJ., Soyer, HP., Button-Sloan, A., et al.[2023]

In a study of 89 patients with axillary lymph node metastases from malignant melanoma, adjuvant radiation therapy combined with surgery achieved an impressive 87% axillary control rate over 5 years, which is better than the 50-70% control rate seen with surgery alone in high-risk cases.

While treatment-related arm edema was common, with 5-year rates of 21% for mild cases and 19% for moderate cases, it was generally manageable, indicating that the benefits of radiation therapy may outweigh the risks of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant irradiation for axillary metastases from malignant melanoma. Ballo, MT., Strom, EA., Zagars, GK., et al.[2022]

In a study of 6,496 melanoma patients diagnosed between 2004 and 2012, those who underwent surgical excision within 6 weeks of diagnosis had a significantly higher 5-year overall survival rate (86%) compared to those who waited more than 90 days (78.6%).

The results suggest that timely surgical intervention is crucial for improving survival outcomes, particularly for patients with Stage 1 melanoma, highlighting the importance of prompt treatment after diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of surgical interval and survival among hospital and non-hospital based patients with melanoma in North Carolina. Adamson, AS., Jackson, BE., Baggett, CD., et al.[2022]

In a clinical trial involving 553 Stage I melanoma patients, immediate node dissection did not show a survival advantage over delayed node dissection, indicating that both approaches are equally effective when patients are monitored regularly.

For patients with melanomas thicker than 2 mm, immediate node dissection is recommended if consistent follow-up every three months cannot be ensured, highlighting the importance of monitoring in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Veronesi, U., Adamus, J., Bandiera, DC., et al.[2019]

Surgical management of melanoma has evolved significantly, with a focus on local control of the primary tumor and the introduction of lymphatic mapping and sentinel lymph node identification, which helps select patients for further treatment.

Surgery remains important not only for controlling the primary tumor but also for palliative care in selected Stage IV melanoma patients with isolated systemic metastases and good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of surgery in the treatment of cutaneous melanoma]. Guggenheim, M., Dummer, R., Giovanoli, P.[2011]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Surgical treatment of malignant melanoma]. [2012]

2. United States pubmed.ncbi.nlm.nih.gov

Surgical management of melanoma. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in melanoma: final results of MSLT-I. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Surgical outcomes of lymph node dissections for stage III melanoma after neoadjuvant systemic therapy are not inferior to upfront surgery. [2023]

5. Ukraine pubmed.ncbi.nlm.nih.gov

[Significance of lymphadenectomy of "sentinel" lymph nodes in combined treatment of cutaneous melanoma localized on extremities and the trunk]. [2023]

6. Australia pubmed.ncbi.nlm.nih.gov

Diagnosis and management of cutaneous melanoma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Adjuvant irradiation for axillary metastases from malignant melanoma. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Association of surgical interval and survival among hospital and non-hospital based patients with melanoma in North Carolina. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[The role of surgery in the treatment of cutaneous melanoma]. [2011]