Melphalan Chemoreduction for Ocular Melanoma

NCT05893654 | Enrolling By Invitation Phase 1 DMC

• 1 other identifier: 48439821100005440
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Uveal Melanoma

Keywords

melanoma; uveal; chemotherapy; chemoreduction; melphalan; ruthenium; brachytherapy

Outcome Measures

Primary Outcomes (1)

• Determination of treatment safety through electroretinography (ERG)

  Participants will undergo ERG exams at baseline, 1, 3, and 6 months after the first intervention. The researchers will assess the patterns of ERG waves to determine whether there are signs of retinal toxicity.

  6 months

Secondary Outcomes (5)

• Reduction of Tumor Size

  6 months

• Best Corrected Visual Acuity (BCVA)

  6 months

• Signs of intraocular inflammation

  6 months

• Treatment-related adverse events

  6 months

• Globe salvage

  12 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Participants will undergo intra-arterial catheterization of the ophthalmic artery, with administration of 7.5mg of melphalan. After 4±1 weeks, they will receive Ru-106 plaque brachytherapy, which will be performed using a 24-mm notched plaque. Due to tumor thickness and the previous IAC, the target dose to the tumor apex shall be as close as possible to 80 Gy, respecting the safety limits regarding the risk of excessive dosage to the tumor base and scleral melting.

Drug: Melphalan Injection; Radiation: Plaque brachytherapy

Interventions

Melphalan Injection DRUG

7.5mg of melphalan injected via intra-arterial catheterization of the ophthalmic artery.

Also known as: Intra-arterial chemotherapy, Chemoreduction

Single Arm

Plaque brachytherapy RADIATION

Brachytherapy will be performed using a 24-mm notched plaque with Ruthenium-106 seeds.

Also known as: Radiation therapy, Plaque brachytherapy with Ruthenium-106

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital das Clínicas de Ribeirão Preto: lead
• Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo: collaborator

Study Sites (1)

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP

Ribeirão Preto, São Paulo, 14040-906, Brazil

Location

Related Publications (14)

• Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol. 2017 Jan 31;11:279-289. doi: 10.2147/OPTH.S89591. eCollection 2017.

  PMID: 28203054 BACKGROUND

• Singh M, Durairaj P, Yeung J. Uveal Melanoma: A Review of the Literature. Oncol Ther. 2018 Jun;6(1):87-104. doi: 10.1007/s40487-018-0056-8. Epub 2018 Feb 6.

  PMID: 32700136 BACKGROUND

• American Brachytherapy Society - Ophthalmic Oncology Task Force. Electronic address: paulfinger@eyecancer.com; ABS - OOTF Committee. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014 Jan-Feb;13(1):1-14. doi: 10.1016/j.brachy.2013.11.008. Epub 2013 Dec 24.

  PMID: 24373763 BACKGROUND

• Reichstein DA, Brock AL. Radiation therapy for uveal melanoma: a review of treatment methods available in 2021. Curr Opin Ophthalmol. 2021 May 1;32(3):183-190. doi: 10.1097/ICU.0000000000000761.

  PMID: 33770014 BACKGROUND

• Parker T, Rigney G, Kallos J, Stefko ST, Kano H, Niranjan A, Green AL, Aziz T, Rath P, Lunsford LD. Gamma knife radiosurgery for uveal melanomas and metastases: a systematic review and meta-analysis. Lancet Oncol. 2020 Nov;21(11):1526-1536. doi: 10.1016/S1470-2045(20)30459-9.

  PMID: 33152286 BACKGROUND

• Marinkovic M, Pors LJ, van den Berg V, Peters FP, Schalenbourg A, Zografos L, Pica A, Hrbacek J, Van Duinen SG, Vu THK, Bleeker JC, Rasch CRN, Jager MJ, Luyten GPM, Horeweg N. Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy. Cancers (Basel). 2021 Dec 13;13(24):6241. doi: 10.3390/cancers13246241.

  PMID: 34944862 BACKGROUND

• Thariat J, Martel A, Matet A, Loria O, Kodjikian L, Nguyen AM, Rosier L, Herault J, Nahon-Esteve S, Mathis T. Non-Cancer Effects following Ionizing Irradiation Involving the Eye and Orbit. Cancers (Basel). 2022 Feb 25;14(5):1194. doi: 10.3390/cancers14051194.

  PMID: 35267502 BACKGROUND

• CREECH O Jr, KREMENTZ ET, RYAN RF, WINBLAD JN. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg. 1958 Oct;148(4):616-32. doi: 10.1097/00000658-195810000-00009. No abstract available.

  PMID: 13583933 BACKGROUND

• Hansson J, Lewensohn R, Ringborg U, Nilsson B. Formation and removal of DNA cross-links induced by melphalan and nitrogen mustard in relation to drug-induced cytotoxicity in human melanoma cells. Cancer Res. 1987 May 15;47(10):2631-7.

  PMID: 3567896 BACKGROUND

• Minor DR, Allen RE, Alberts D, Peng YM, Tardelli G, Hutchinson J. A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer. 1985 Jun 1;55(11):2638-44. doi: 10.1002/1097-0142(19850601)55:113.0.co;2-e.

  PMID: 3995475 BACKGROUND

• Shields CL, Jorge R, Say EA, Magrath G, Alset A, Caywood E, Leahey AM, Jabbour P, Shields JA. Unilateral Retinoblastoma Managed With Intravenous Chemotherapy Versus Intra-Arterial Chemotherapy. Outcomes Based on the International Classification of Retinoblastoma. Asia Pac J Ophthalmol (Phila). 2016 Mar-Apr;5(2):97-103. doi: 10.1097/APO.0000000000000172.

  PMID: 26765038 BACKGROUND

• Karydis I, Gangi A, Wheater MJ, Choi J, Wilson I, Thomas K, Pearce N, Takhar A, Gupta S, Hardman D, Sileno S, Stedman B, Zager JS, Ottensmeier C. Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease. J Surg Oncol. 2018 May;117(6):1170-1178. doi: 10.1002/jso.24956. Epub 2017 Dec 28.

  PMID: 29284076 BACKGROUND

• Francis JH, Abramson DH, Gobin YP, Marr BP, Dunkel IJ, Riedel ER, Brodie SE. Electroretinogram monitoring of dose-dependent toxicity after ophthalmic artery chemosurgery in retinoblastoma eyes: six year review. PLoS One. 2014 Jan 20;9(1):e84247. doi: 10.1371/journal.pone.0084247. eCollection 2014.

  PMID: 24465398 BACKGROUND

• Robson AG, Frishman LJ, Grigg J, Hamilton R, Jeffrey BG, Kondo M, Li S, McCulloch DL. ISCEV Standard for full-field clinical electroretinography (2022 update). Doc Ophthalmol. 2022 Jun;144(3):165-177. doi: 10.1007/s10633-022-09872-0. Epub 2022 May 5.

  PMID: 35511377 BACKGROUND

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Melphalan; Brachytherapy; Radiotherapy; Ruthenium-106

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Therapeutics

Study Officials

• Rodrigo Jorge, MD, PhD

  Professor of Ophthalmology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 8, 2023
• Study Start: May 1, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Starting immediately after publication, for an unlimited time.
• Access Criteria: Open access.

Locations

BR (1)