Carbon Ion Radiation Therapy in the Treatment of Mucous Melanomas of the Female Lower Genital Tract

Study Overview
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Brief Summary
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The present monocentric prospective phase 2 study aims to reproduce the results obtained at NIRS thus offering the possibility of obtaining a promising rate of progression-free survival (PFS) and local control (LC) in patients diagnosed with mucosal melanoma of lower genital tract. Systemic treatment with immunotherapy is not the subject of this study but is allowed both in the neoadjuvant and sequential regimens. Melanomas have always been considered poorly radiosensitive. It is now accepted that high LET (Linear Energy Transfer) particle beams, such as carbon ions, can offer a biological advantage, compared to photons treatment, in radio-resistant neoplasms treatment, thanks to their higher biological efficacy (RBE) against tumours with a low α/ ß ratio. In addition, carbon ions have the physical advantage of an inverted depth deposition profile compared to photons, allowing then a steep dose gradients that ensure increased sparing of adjacent healthy organs at risk (OARs).

Detailed Description
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Patients with primary gynaecological melanoma, non-metastatic, non-suitable for surgery, and not previously subjected to conventional radiotherapy can be enrolled in the trial, according to selection criteria. After requested baseline exams, the patient undergoes to simulation phase for the carbon ion radiation therapy, according to study constraints. The patient will then receive immunotherapy not concomitant to CIRT. The response is evaluated through RECIST criteria. PFS is the primary endpoint, calculated from the end of CIRT to date of disease progression or death or last follow up.

Official Title
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CNAO 40-2020 C CYCLE Carbon Ion Radiation Therapy in the Treatment of Mucous Melanomas of the Female Lower Genital Tract Radioterapia Con Ioni Carbonio Per il Trattamento Dei Melanomi Mucosi Ginecologici

Conditions
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Malignant Melanoma, Gynecologic Cancer

Intervention / Treatment
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* Radiation: carbon ion radiation therapy CIRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis Absence of skin extension N + (only if confined to the groin and pelvis) Age between 20-80 years ECOG 0-2 No evidence of metastasis At least 5 mm away with rectum and bladder wall No previous RT Written informed consent Patient's ability to understand the characteristics and consequences of the clinical trial Molecular characterization/ mutational state Disease staging (baseline exams) Exclusion Criteria: Hip prosthesis, or metal prostheses or any other condition that prevents adequate imaging to identify the target volume and calculate the dose in the treatment plan Psychic or other disorders that may prevent informed consent Previous invasive tumor unless patient has been disease free for at least 3 years Contraindication to MRI Pregnancy or breastfeeding in progress

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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
Interventional Model Description: cohort of 9 patients with primary gynecological melanoma. The intervention consists in carbon ion radiation therapy. The expected duration of treatment is 4 weeks, 4 fractions per week.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carbon ion radiotherapy<br>Patients affected by pelvic recurrence of gynecological cancer, who had not undergone to previous pelvic irradiation, will be enrolled on this study. After enrollment, patients undergo baseline exams, simulation CT and MRI and then carbon ion radiation therapy treatment will be performed, according to trial indications. | Radiation: carbon ion radiation therapy CIRT<br>* CIRT: The low-dose CTV (clinical target volume) will receive a total dose of 43 GyRBE in 10 fractions, 4 fractions per week. The high-dose CTV will receive a total dose of 68.8 GyRBE in 16 fractions, 4 fractions per week. The expected duration of treatment is 4 weeks, 4 fractions per week. Treatments lasting longer than 6 weeks, or with less than 6 fractions administered on 14 consecutive days, will not be considered acceptable. Immunotherapy: Patients will undergo immunotherapy after carbon ion radiation therapy (CIRT) up to maximum response and/or up to tolerance. The concomitant association of immunotherapy is not envisaged in this protocol.<br>* Other names: immunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | estimate 2-year PFS in patients diagnosed with mucosal melanoma of the lower genital tract, treated with carbon ion radiation therapy. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The OS will be calculated from the end date of therapy with carbon ion radiation | 3 years | 
| Toxicity according to Common Terminology Criteria for Adverse Events (CTCAE version 5.0) | acute, medium term and late toxicity | within 3 months, 3-6 months, over 6 months from CIRT | 
| local response | according to Response Evaluation Criteria in Solid Tumours RECIST 1.1 | 3 years | 
| assessment of quality of life | assessed through questionarie Portec 3 administered on each follow up | 3 years | 
| assessment of quality of life for >= 75 years old patients | assessed through questionnaire G8 Geriatric questionnaire administered on each follow up | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hadrontherapy, gynecological melanoma