Evaluation of Intra-Arterial Chemotherapy with Topotecan and Drug Combination for Conservative Management of Retinoblastoma in Eligible Patients

The primary objective of the study titled "RETINO 2018: conservative treatment for **retinoblastoma**: efficacy of the new management strategies and visual outcome" is to evaluate the efficacy of intra-arterial chemotherapy (IAC) in terms of local control of the disease in patients eligible for IAC. This is a randomized phase II study. The clinical relevance of this objective lies in its potential to improve local disease control, which is crucial for preserving the eye and vision in patients with retinoblastoma. Additionally, the study aims to assess the visual function, based on World Health Organization (WHO) criteria, in patients eligible for other conservative treatments, such as intravenous chemotherapy in combination with local ophthalmologic treatments or local ophthalmological treatment without intravenous chemotherapy. This aspect of the study is a minimally invasive interventional study, focusing on the visual outcomes of these conservative treatment strategies.

The clinical trial focuses on evaluating **ocular conservative treatment for retinoblastoma**. The study population includes both male and female participants, with an age range from 6 months to 6 years. The trial involves a vulnerable population, as it includes children diagnosed with retinoblastoma. The sponsor has not provided the total number of participants. Participants were selected based on specific inclusion criteria, such as being newly diagnosed with retinoblastoma and having at least one eye eligible for conservative management. Additionally, participants must not have received prior chemotherapy or radiotherapy for any cancer and must have no contraindications to the proposed treatments. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study aims to assess the efficacy of intra-arterial chemotherapy (IAC) and other conservative treatments in managing the disease, with a focus on local control and visual function based on World Health Organization criteria.

The clinical trial is designed to evaluate the efficacy of new management strategies for **retinoblastoma**, focusing on ocular conservative treatment. This trial is structured as a randomized, double-blind, controlled study, with an estimated duration extending until January 2034. The trial is divided into two studies: Study 1 aims to assess the efficacy of intra-arterial chemotherapy (IAC) in terms of local disease control, while Study 2 evaluates visual function based on World Health Organization criteria in patients eligible for other conservative treatments. The primary endpoint for Study 1 is the rate of eye preservation 24 months post-randomization, comparing the investigational arm (Topotecan + Melphalan) with the reference arm (Melphalan). For Study 2, the primary endpoint is the percentage of patients with varying degrees of visual impairment at age six, with at least 24 months of follow-up.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as newly diagnosed retinoblastoma, eligibility for conservative management, and compliance with study requirements. Follow-up visits will be scheduled to monitor treatment efficacy and safety, with the end-of-study visit marking the conclusion of the participant's involvement. The expected length of participant involvement is at least 24 months, with conditions for early termination including non-compliance, adverse events, or withdrawal of consent. The trial will utilize various pharmaceutical forms, including solutions for infusion and injection, with administration routes such as intra-arterial and intravenous use. The study will not involve pediatric formulations, and all active substances are of chemical origin. Participants will be monitored closely to ensure adherence to the protocol and to evaluate the outcomes of the conservative treatment strategies.

The clinical trial involves the administration of several **experimental medications** for the treatment of retinoblastoma. The first medication is **TOPOTECAN**, marketed as "TOPOTECANE ACCORD 1 mg/ml, solution à diluer pour perfusion" and "Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion." This medication is provided in a **solution for infusion** form and is administered via **intraarterial use**. The active substance, topotecan, is of chemical origin and is produced by Accord Healthcare France SAS and Pfizer Europe MA EEIG.

**VINCRISTINE SULFATE** is another experimental medication used in the trial, marketed as "VINCRISTINE HOSPIRA 2 mg/2 ml, solution injectable." It is available as a **solution for injection** and is administered **intravenously**. The active substance is of chemical origin, manufactured by Pfizer Holding France.

**ETOPOSIDE** is included in the trial under the product name "Etoposide 20 mg/ml concentrate for solution for infusion." This medication is provided as a **solution for infusion** and is administered **intravenously**. The active substance is chemically derived and produced by Medac Gesellschaft für klinische Spezialpräparate mbH (Wedel).

**CARBOPLATIN** is administered as "CARBOPLATINE HOSPIRA 10 mg/ml, solution injectable pour perfusion." It is available as a **solution for injection/infusion** and is administered **intravenously**. The active substance is of chemical origin, manufactured by Pfizer Holding France.

**MELPHALAN HYDROCHLORIDE** is used in the trial under the product name "MELPHALAN TILLOMED 50 mg/10 mL, poudre et solvant pour solution injectable / pour perfusion." This medication is provided as a **solution for injection/infusion** and is administered via **direct intravenous injection**. The active substance is chemically derived and produced by Tillomed Pharma GmbH.

All medications in this trial are not pediatric formulations and are classified as chemical substances. The trial does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedules is monitored throughout the study to ensure adherence to the treatment protocol.

The efficacy of the clinical trial titled "RETINO 2018: conservative treatment for retinoblastoma: efficacy of the new management strategies and visual outcome" will be assessed through two primary endpoints. In Study 1, the primary endpoint is the rate of eye preservation in the investigational arm (Topotecan + Melphalan) compared to the reference arm (Melphalan) 24 months after the date of randomization. This will evaluate the efficacy of intra-arterial chemotherapy (IAC) in terms of local control of the disease in patients eligible for IAC. In Study 2, the primary endpoint is the percentage of patients with major, mild, or no impairment of visual function according to World Health Organization (WHO) criteria. This assessment will be based on normal bilateral visual acuity (≥ 6/10) or mild bilateral visual impairment (3/10 to 5/10) according to tumor location and extension, when the patient reaches 6 years of age and has at least 24 months of follow-up after study inclusion.