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

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"

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).

Study Overview

• Status: Recruiting
• Conditions: Gynecologic Cancer; Malignant Melanoma
• Intervention / Treatment: Radiation: carbon ion radiation therapy CIRT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amelia Barcellini, MD; Phone Number: 0039 0382078501; Email: amelia.barcellini@cnao.it

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • CNAO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: carbon ion radiotherapy; 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; 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.; Other Names: immunotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CNAO National Center of Oncological Hadrontherapy

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: hadrontherapy, gynecological melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: CNAO 40-2020 C CYCLE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No