Adjuvant Radiation Therapy in Treating Patients With Resected Desmoplastic Melanoma

Study Overview
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Brief Summary
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This phase II trial is studying how well adjuvant radiation therapy works in treating patients who have undergone surgery for desmoplastic melanoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy after surgery may kill any tumor cells remaining after surgery.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the recurrence rates in patients with desmoplastic melanoma (DM) >= 1 mm deep treated with adjuvant radiotherapy after surgical resection. II. Assess recurrence rates in patients with locally recurrent DM treated with adjuvant radiotherapy after surgical resection. SECONDARY OBJECTIVES: I. Evaluate the impact of adjuvant radiation therapy after surgical resection on disease free and overall survival. II. Evaluate the immediate and long-term morbidity of the addition of radiotherapy to surgery. OUTLINE: Within 8 weeks after surgical resection, patients undergo radiation therapy twice weekly over approximately 2.5 weeks for a total of 5 fractions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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Phase II Trial Evaluating Resection Followed By Adjuvant Radiation Therapy (RT) For Patients With Desmoplastic Melanoma

Conditions
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Recurrent Melanoma

Intervention / Treatment
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* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 Pathologically proven DM >= 1 mm in depth or locally recurrent DM; recurrent tumor is defined as a tumor found =< 2 cm from the previous excision or within the surgical bed (which includes the extent of previous skin flaps) DM resected with pathologically negative margins; acceptable surgery includes standard wide local excision and Moh's surgery Tumors on the trunk proximal extremities need to have a >= 2 cm negative margin; tumors located on the head and neck and distal extremities will have an attempt at 2 cm negative margins but due to location and subsequent concern regarding cosmesis a margin < 2 cm will be acceptable if margin is negative Margins from tumors resected using the Moh's technique will be accepted if negative and best approximation of tumor width will be made Radiation therapy (RT) is to begin =< 8 weeks after definitive surgical resection Adjuvant systemic therapy (immunotherapy or chemotherapy) must be postponed until irradiation is completed Exclusion Criteria Previous irradiation to the same site Non-healing surgical wound Active infection at the surgical site Evidence of metastatic disease; local nodal disease is still eligible for the trial Life expectancy < 1 year Melanoma with focally desmoplastic features, in which the desmoplastic melanoma is not the predominant histologic pattern of the tumor, will be excluded; non-desmoplastic neurotropic melanoma and non-desmoplastic spindle cell melanoma are also excluded Previous malignancy < 5 years excluding basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ (with the exception of patients who have stage I breast cancer who were adequately treated with adjuvant therapy and are currently disease free, and patients with stage I or II prostate cancer treated with prostatectomy or radiotherapy and are biochemically free of disease [for radical retropubic prostatectomy (RRP) prostate-specific antigen (PSA) < 0.3 and for radiotherapy PSA < 2.0 above the post treatment nadir]) Any of the following: Pregnant women Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (adjuvant radiation therapy)<br>Within 8 weeks after surgical resection, patients undergo radiation therapy twice weekly over approximately 2.5 weeks for a total of 5 fractions in the absence of disease progression or unacceptable toxicity. | Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Local Recurrence Rate (LRR)/Incidence of Local Recurrence | The primary endpoint is the incidence of local recurrence within 2 years after treatment. Local recurrence (LR) is defined as a desmoplastic melanoma lesion recurring within the radiated field. The properties of the binomial distribution will be used to construct a 95% confidence interval for the true 2-year local recurrence rate (LRR). The Kaplan-Meier method will be used if some patients are lost to follow-up. | Within 2 years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Regional and Systemic Metastases | Incidence of regional and systemic metastasis: Incidences will be calculated for each cohort and 95% confidence intervals will be constructed using the properties of the binomial distribution. | Up to 5 years | 
| Survival Time | Survival time: Survival time is defined as the time from randomization to death due to any cause. The median survival time will be estimated using the method of Kaplan-Meier. | up to 5 years | 
| Failure Time | Failure time is defined as the time from randomization to death due to any cause or disease progression. The median failure time will be estimated using the method of Kaplan-Meier. | Time from randomization to death due to any cause or disease progression (up to 5 years) | 
| Toxicity | For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. The number of participants reporting a grade 3 or higher toxicity are reported. For a list of all reported adverse events, please refer to the Adverse Events Section below. | Up to 5 years | 
| Change in Fatigue From Baseline to 3 Months as Assessed by the Brief Fatigue Inventory | Fatigue Assessment: A portion of the Brief Fatigue Inventory will be used to determine fatigue changes throughout the course of radiation. Patients will fill out the questionnaire at baseline, weekly during radiation, and 3 months after the beginning of radiation. Fatigue will be defined as: minor if the patient answers 0-3 (on a 10 point scale), mild for answers of 4-6, and severe for answers of 7-10. The percentage of patients that have worsened (improved) fatigue from baseline to the radiation stage will be calculated. We will also compare fatigue levels at baseline to the 3 month visit. Worsened fatigue is defined as going from minor to mild, minor to severe, or mild to severe. Improved fatigue is defined as going from severe to mild, severe to minor, or mild to minor. | Baseline to up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage I melanoma, stage II melanoma, stage III melanoma