Clinical Trial Evaluating Doxorubicin Hydrochloride, Fluorouracil, and Oxaliplatin in Pediatric Hepatoblastoma and Hepatocarcinoma Treatment

The primary objective of this clinical trial is to evaluate the potential for **individualizing treatment** of malignant liver tumors in children, specifically **hepatoblastoma** and **hepatocarcinoma**, by classifying them into different groups based on the stage of the disease. This stratification aims to optimize therapeutic approaches, potentially reducing the occurrence of treatment side effects without significantly impacting the cure rate. Additionally, the study seeks to improve the overall curability of these conditions, particularly in cases where current therapies are insufficient, and to identify the most effective surgical treatment methods. These objectives are clinically relevant as they address the need for tailored treatment strategies that could enhance patient outcomes and minimize adverse effects.

Secondary objectives include the identification of biological features and genetic determinants of liver cancer, which could provide insights into the disease's pathogenesis and inform future therapeutic targets. Furthermore, the study aims to modify the classification of liver tumors in children, potentially leading to more precise diagnostic and treatment protocols.

The clinical trial involves participants diagnosed with **hepatoblastoma** or liver cancer (hepatocarcinoma), focusing on a vulnerable population under the age of 30. Both male and female subjects are included in the study. The trial aims to explore the potential for individualized treatment based on disease stage, reduce treatment side effects, and improve overall curability. Participants were selected based on clinical signs of malignant liver tumors and the provision of informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the treatment of **hepatoblastoma** and **hepatocarcinoma** in children and adolescents. This study is a Phase 3, therapeutic confirmatory trial, employing a randomized, double-blind, controlled methodology. The trial aims to individualize treatment based on disease stage, reduce treatment side effects, improve curability, and select effective surgical methods. The trial is expected to run from June 2023 to September 2027, with participant involvement lasting up to 140 days, depending on the treatment regimen.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on clinical signs of **hepatoblastoma** or **hepatocarcinoma**, age under 30, and informed consent. The trial includes multiple follow-up visits to monitor treatment response, adherence to surgical guidelines, and chemotherapy-related toxicity. The end-of-study visit will assess primary endpoints such as event-free survival, overall survival, and surgical resectability.

The trial involves the administration of various chemotherapeutic agents, including **doxorubicin hydrochloride**, **fluorouracil**, **oxaliplatin**, **cisplatin**, **sorafenib tosilate**, **irinotecan hydrochloride**, **etoposide**, **sodium thiosulfate**, **gemcitabine hydrochloride**, **vinorelbine**, and **carboplatin**. These agents are administered intravenously, except for **sorafenib tosilate**, which is given orally. The maximum treatment period varies by drug, with the longest being 140 days for **carboplatin**.

Participants may be terminated early from the study if they experience unacceptable toxicity, non-compliance with the study protocol, or withdrawal of consent. The trial's primary endpoints include event-free survival, overall survival, and chemotherapy-related toxicity, with secondary endpoints focusing on surgical outcomes and treatment response. The study aims to enhance the understanding and management of malignant liver tumors in the pediatric population.

The clinical trial involves the administration of several **chemotherapeutic** agents and a **protein kinase inhibitor**. **Doxorubicin hydrochloride** is administered intravenously with a maximum daily dose of 60 mg and a total dose of 720 mg over a treatment period of 126 days. The pharmaceutical form is coded as PHF00231MIG.

**Fluorouracil** is also administered intravenously, with a maximum daily dose of 1200 mg and a total dose of 7200 mg over 126 days. It shares the same pharmaceutical form code as doxorubicin, PHF00231MIG.

**Oxaliplatin** is delivered intravenously, with a maximum daily dose of 200 mg and a total dose of 800 mg over a 60-day period. The pharmaceutical form is PHF00230MIG.

**Cisplatin** is administered intravenously, with a maximum daily dose of 200 mg and a total dose of 1200 mg over 84 days. The pharmaceutical form is PHF00015MIG.

**Sorafenib tosilate**, a **protein kinase inhibitor**, is administered orally with a maximum daily dose of 400 mg and a total dose of 40000 mg over 100 days. The pharmaceutical form is PHF00082MIG.

**Irinotecan hydrochloride** is administered intravenously, with a maximum daily dose of 100 mg and a total dose of 1500 mg over 126 days. The pharmaceutical form is PHF00230MIG.

**Etoposide** is delivered intravenously, with a maximum daily dose of 400 mg and a total dose of 2400 mg over 126 days. The pharmaceutical form is PHF675.

**Sodium thiosulfate**, marketed as Pedmark, is administered intravenously as a solution for infusion. The maximum daily dose is 25.6 g, with a total dose of 204.8 g over 84 days.

**Gemcitabine hydrochloride** is administered intravenously, with a maximum daily dose of 2000 mg and a total dose of 8000 mg over 60 days. The pharmaceutical form is PHF00230MIG.

**Vinorelbine**, referred to as vincristine in the trial, is administered intravenously, with a maximum daily dose of 2 mg and a total dose of 36 mg over 126 days. The pharmaceutical form is PHF00007MIG.

**Carboplatin** is administered intravenously, with a maximum daily dose of 1000 mg and a total dose of 10000 mg over 140 days. The pharmaceutical form is PHF00230MIG.

Participant compliance is monitored through regular assessments and adherence checks to ensure accurate dosing and administration throughout the trial period.

The efficacy of the clinical trial will be assessed using a range of primary endpoints tailored to the study group. These endpoints include event-free survival, overall survival, adherence to surgical guidelines, chemotherapy-related toxicity, hearing loss, response, failure-free survival, and surgical resectability. These parameters are critical in evaluating the effectiveness of the treatment regimens being tested in children and adolescents with primary malignant liver cancer, specifically **Hepatoblastoma** and **Hepatocarcinoma**.

The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial. The trial is designed to individualize treatment based on the stage of the disease, aiming to improve curability and reduce treatment side effects without compromising the cure rate. The trial will also focus on selecting the most effective surgical treatment methods. The trial is expected to conclude by September 29, 2027, with recruitment having started on June 1, 2023.