Trial Title:
Melphalan Chemoreduction for Ocular Melanoma
NCT ID:
NCT05893654
Condition:
Uveal Melanoma
Conditions: Official terms:
Melanoma
Melphalan
Conditions: Keywords:
melanoma
uveal
chemotherapy
chemoreduction
melphalan
ruthenium
brachytherapy
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Enrolling by invitation
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Melphalan Injection
Description:
7.5mg of melphalan injected via intra-arterial catheterization of the ophthalmic artery.
Arm group label:
Single Arm
Other name:
Intra-arterial chemotherapy
Other name:
Chemoreduction
Intervention type:
Radiation
Intervention name:
Plaque brachytherapy
Description:
Brachytherapy will be performed using a 24-mm notched plaque with Ruthenium-106 seeds.
Arm group label:
Single Arm
Other name:
Radiation therapy
Other name:
Plaque brachytherapy with Ruthenium-106
Summary:
The goal of this clinical trial is to investigate a new approach for treating large uveal
melanomas, a type of eye cancer. The study aims to determine the effectiveness of using
intra-arterial melphalan, a chemotherapy drug, to reduce tumor thickness, allowing for
subsequent radiation therapy using a Ru-106 plaque.
The main questions this trial seeks to answer are:
- Can intra-arterial melphalan effectively reduce the thickness of large uveal
melanomas?
- Is the combination of intra-arterial melphalan and brachytherapy a safe and
effective treatment option for these tumors?
Participants enrolled in the trial have clinically diagnosed choroidal melanoma with
tumor thickness equal to or greater than 8.00 mm. They will undergo a procedure where the
chemotherapy drug is injected directly into the blood vessels that supply the tumor.
After a few weeks, they will receive the radiation treatment using a small device placed
on the eye. Throughout the trial, participants will have different tests to monitor the
tumor and their vision, such as ultrasound scans, pictures of the inside of the eye, and
a test called electroretinography (ERG) to check the function of the retina. These tests
will be done at the start of the trial and at 1, 3, and 6 months later to track the
progress of the treatment.
Detailed description:
INTRODUCTION Choroidal melanoma is the most common primary intraocular malignancy in
adults, thus being the focus of extensive research. The primary treatment goals of this
disease consist in controlling local disease, reducing the risk of distant metastases,
and avoiding enucleation whenever possible.
Plaque brachytherapy is currently the standard treatment for small and medium-sized uveal
melanomas. In clinical practice, ruthenium (Ru-106) or iodine (I-125) are the most
commonly employed radioisotopes. Ruthenium is the most utilized radioisotope in Europe
and South America due to its availability and good clinical outcomes. It is currently the
only available option in Brazil's public health system (SUS). However, its use for large
tumors (greater than 10 mm in thickness and/or 22 mm in diameter) is limited by the
inability of delivering an adequate therapeutic dose of radiation without causing further
damage to the surrounding retinal tissue.
For this reason, researchers in medical physics have been investigating new treatment
options in the last decades, including external beam radiotherapy (EBRT), radiosurgery
(gamma knife or linear accelerator), and proton beam therapy. Although gamma knife
radiosurgery and proton beam therapy are effective treatments with reliable tumor control
rates, they are associated with poor visual outcomes, inadequate globe retention, and
their use is reportedly limited in public health systems of low- or middle-income
countries. EBRT carries potential side effects related to a broader radiation field, with
an increased risk for complications in ocular and periocular structures, such as eyelids,
sclera, lens, and retina. Finally, enucleation is an effective management for very large
tumors, but it is usually a last resource.
Considering the above-mentioned treatment limitations for large choroidal melanomas, our
group explored an alternative approach using intra-arterial melphalan for tumor
chemoreduction, aiming to reduce thickness and allow subsequent brachytherapy using a
Ru-106 plaque.
Intra-arterial chemotherapy (IAC) with melphalan has been used to treat multiple cancers,
including liver metastases from uveal and skin melanomas, but it has never been described
as a primary tumor treatment. Previous studies have demonstrated a reasonable safety
profile of the therapy when used for the treatment of other tumors.
This is a phase I clinical trial that assesses the safety profile of chemoreduction with
intra-arterial melphalan, followed by ruthenium brachytherapy, performed in patients that
would otherwise need enucleation due to tumor size.
METHODS Patients enrolled in the trial shall have clinically diagnosed choroidal melanoma
with tumor thickness equal to or greater than 8.00 mm. IAC with 7.5 mg of melphalan will
be performed through selective catheterization of the ophthalmic artery followed by
Ru-106 plaque brachytherapy 4±1 weeks after the IAC. All patients will be followed up
with baseline and subsequent B-scan ultrasonography, SD-OCT studies, color fundus
pictures, infrared photographs, and electroretinograms (ERG).
Baseline and follow-up visits At baseline, patients will undergo a comprehensive
ophthalmologic examination including ETDRS best-corrected visual acuity (BCVA), slit lamp
biomicroscopy, indirect ophthalmoscopy, spectral-domain optical coherence tomography
(SD-OCT), electroretinogram (ERG) performed according to the recommendations of the
International Society for Clinical Electrophysiology of Vision (ISCEV) standard,14 and
ocular B-scan ultrasound.
OCT examinations will be performed using the Spectralis® HRA+OCT image system (Heidelberg
Engineering, Germany). The OCT scan center will be determined at baseline based on
patient fixation. In subsequent visits, the automatic follow-up from the Heidelberg
machine will be used to scan the same region from the initial visit. Scans over the
lesions located close to the posterior pole will also be performed.
Ocular ultrasound will be performed using the Accutome 4sight device in mode B, in the
initial consultation, and in 1 month, 3 months, and 6 months after the intervention. The
examination will take place with the patient in a seated position, in the most ergonomic
and comfortable way as possible, respecting the individual characteristics of the
participants.
After the initial assessment, confirmation of the signature of the informed consent,
explanation about the procedure, and verbal consent, IAC will be performed in a surgical
environment. The intraarterial injection of 7.5 mg of melphalan will be performed only
once, in the ophthalmic artery corresponding to the eye affected by choroidal melanoma.
Chemotherapy infusion will be performed directly into the ostium of the ophthalmic artery
through a microcatheter guided by fluoroscopy via the femoral artery. The drug will be
infused in a slow pulsatile manner for 30 minutes to avoid backflow of chemotherapy and
arterial occlusion.
After 4±1 weeks, Ru-106 brachytherapy will be performed using a 24-mm notched plaque. Due
to tumor thickness and previous IAC, the target dose to the tumor apex should be the
closest possible to 80 Gy, respecting the safety limits regarding the risk of excessive
dosage to the tumor base and scleral melting.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age equal to or higher than 18 years
- Diagnosis of choroidal melanoma with a thickness equal to or higher than 8 mm on
ultrasound evaluation
- Comprehension and signature of the informed consent
- Adequate pupil dilation and sufficient cooperation to carry out the complementary
exams
Exclusion Criteria:
- Choroidal melanomas with a greatest basal diameter higher than 18mm
- Any clinical condition that impairs fundus documentation or patient follow-up
- Medical or psychological conditions that prevent comprehension and signature of the
informed consent
- Pregnancy, breastfeeding, or plans of getting pregnant in the next year
- Past medical history of allergic reactions or hypersensitivity to melphalan
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP
Address:
City:
Ribeirão Preto
Zip:
14040-906
Country:
Brazil
Start date:
May 1, 2021
Completion date:
June 2024
Lead sponsor:
Agency:
Hospital das Clínicas de Ribeirão Preto
Agency class:
Other
Collaborator:
Agency:
Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Agency class:
Other
Source:
Hospital das Clínicas de Ribeirão Preto
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05893654
