Nodal Radiation Therapy for Sentinel Lymph Node Positive Melanoma

Study Overview
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Brief Summary
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This phase II trial seeks to determine the role of nodal radiation therapy after sentinel lymph node biopsy (SLNB) for patients with high risk sentinel lymph node positive melanoma who are planned for immunotherapy without completion lymph node dissection. Prior studies of patients with more advanced melanoma have shown nodal radiation therapy can decrease the risk of nodal recurrence but it is not known if this same benefit will be seen in patients with high risk sentinel lymph node positive disease who are planned for immunotherapy.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine if regional nodal radiation therapy prolongs the time to regional recurrence. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive adjuvant immunotherapy and nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks). GROUP II: Patients receive adjuvant immunotherapy alone. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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The Role of Nodal Radiation Therapy in Sentinel Lymph Node Positive Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Other: Immunotherapy
* Other: Quality-of-Life Assessment
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be planned for post-operative immunotherapy No evidence of distant metastasis as determined by clinical examination and any form of imaging No evidence of clinically involved lymph nodes prior to SLNB Pathologically confirmed sentinel lymph node positive melanoma with high risk features (extracapsular extension [ECE] or 0.5 mm+ nodal tumor implant or 2+ involved nodes or lymphovascular invasion of the primary tumor) Has provided written informed consent for participation in this trial Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less Life expectancy greater than 6 months Patients capable of childbearing are using adequate contraception Available for follow-up Exclusion Criteria: Complete lymph node dissection (CLND) of the nodal basin containing the positive SLN Distant metastasis Previous radiation therapy (RT) to the nodal area planned for RT such that the prior RT field would be included in the current treatment field. In other words, treatment on this trial would require re-irradiation of tissues Women who are pregnant Adults unable to consent, individuals who are not yet adults, pregnant women and prisoners will be excluded from this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (immunotherapy, radiation therapy)<br>Within 12 weeks of SLNB, patients start nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks). Immunotherapy planned to begin at any time after SLNB. | Other: Immunotherapy<br>* All patients must be planned for treatment with any immunotherapy agent after sentinel lymph node biopsy (e.g. pembrolizumab or nivolumab). For patients receiving radiation therapy initiation may be before, during or after radiation.<br>* Other names: Immunologically Directed Therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Radiation: Radiation Therapy<br>* Undergo nodal radiation therapy<br>* Other names: Therapy, Radiation;|
| Active Comparator: Group II (immunotherapy)<br>Patients planned to undergo immunotherapy. | Other: Immunotherapy<br>* All patients must be planned for treatment with any immunotherapy agent after sentinel lymph node biopsy (e.g. pembrolizumab or nivolumab). For patients receiving radiation therapy initiation may be before, during or after radiation.<br>* Other names: Immunologically Directed Therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to regional nodal recurrence | Regional nodal recurrence will be assessed by physical exam and routine surveillance imaging during follow-up | From date of sentinel lymph node biopsy, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to locoregional recurrence | Local recurrence, locoregional recurrence (including both regional recurrence and local recurrence at the primary tumor site) will also be assessed by physical exam and routine surveillance imaging during follow-up. | From date of sentinel lymph node biopsy, assessed up to 5 years | 
| Time to distant metastasis | Distant metastasis will also be assessed by physical exam and routine surveillance imaging during follow-up. | From date of sentinel lymph node biopsy, assessed up to 5 years | 
| Progression-free survival |  | From date of sentinel lymph node biopsy to recurrence event or last follow-up, assessed up to 5 years | 
| Overall survival |  | From date of sentinel lymph node biopsy to last follow-up, assessed up to 5 years | 
| Incidence of long term toxicity | Long term toxicity including lymphedema, infection, decreased mobility will be assessed at the time of routine follow up appointments. Physician-reported toxicity related to regional nodal disease or treatment will be recorded as per Common Terminology Criteria for Adverse Events version 5.0. Specific toxicity to be evaluated will include: fatigue, localized edema, lymphedema, pain, skin infection, soft tissue infection, thrush, radiation recall reaction, arthritis, fibrosis, joint range of motion, dysphagia, dysgeusia and dry skin. | Up to 5 years | 
| Patient reported quality of life | Quality of life in all patients will be assessed by Functional Assessment of Cancer Therapy General survey. Patients with head and neck nodal disease will also be assessed by the University of Washington Quality of Life survey and patients with axillary nodal disease will also be assessed by the Lymphoedema Quality of Life-ARM. | At baseline, 3 months after sentinel lymph node biopsy, 9 months after sentinel lymph node biopsy, and 2 years after sentinel lymph node biopsy |