Comparison of Neoadjuvant Radiochemotherapy Versus Chemotherapy in Locally Advanced Resectable Gastroesophageal Junction Adenocarcinoma Using Fluorouracil, Docetaxel, Oxaliplatin, and Calcium Folinate

The primary objective of the RACE-trial is to evaluate whether the addition of preoperative **radiochemotherapy** is superior to perioperative chemotherapy alone in improving progression-free survival for patients with resectable adenocarcinoma of the gastroesophageal junction (GEJ). This is clinically relevant as it aims to enhance treatment outcomes for patients undergoing oncologically adequate surgery, specifically D2 resection and appropriate mediastinal lymphadenectomy. The study focuses on patients with locally advanced, potentially resectable adenocarcinoma of the GEJ, classified as AEG type I-III.

The clinical trial involves participants diagnosed with **adenocarcinoma of the gastroesophageal junction** (AEG type I-III). The study population includes both male and female subjects, aged 18 years and above, who are candidates for potential curative resection. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria emphasize adequate hematologic, liver, and renal function, as well as specific coagulation parameters. Participants must have a histologically proven, locally advanced, and potentially resectable form of the disease, with no distant metastasis. Lifestyle considerations such as diet and physical activity are not detailed in the available data. The trial includes a vulnerable population, but specific details regarding this aspect are not disclosed.

The clinical trial is designed to evaluate the efficacy of **neoadjuvant radiochemotherapy** compared to chemotherapy alone in patients with locally advanced, potentially resectable **adenocarcinoma of the gastroesophageal junction**. This is a randomized, multicenter, open-label, phase III study. The primary endpoint is to assess whether the addition of preoperative radiochemotherapy improves progression-free survival in patients undergoing oncologically adequate surgery. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumor relapse, perioperative morbidity and mortality rate, safety and toxicity, and quality of life assessments.

The trial involves the administration of **fluorouracil**, **docetaxel**, **oxaliplatin**, and **calcium folinate**, all delivered via intravenous use. The maximum treatment period for each participant is 33 weeks. The study is expected to conclude by June 2025, with recruitment having commenced in June 2020. Participants will be involved in the study for the duration of the treatment period, with regular follow-up visits to monitor their health status and response to treatment.

The sequence of study visits begins with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven adenocarcinoma, adequate organ function, and performance status. Follow-up visits will occur at regular intervals to assess treatment efficacy and monitor for adverse events. The end-of-study visit will evaluate the overall outcomes and gather final data on the primary and secondary endpoints.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, any deviation from the inclusion criteria or failure to adhere to the study protocol may result in early termination from the trial. The study is conducted in accordance with ethical guidelines, ensuring informed consent is obtained from all participants prior to randomization.

The clinical trial involves the administration of several **experimental medications** for the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. The first medication, **Fluorouracil**, is provided as a solution for injection. It is administered intravenously with a maximum daily dose of 2600 mg/m² and a total maximum dose of 23475 mg/m² over a treatment period of up to 33 days. The chemical origin of Fluorouracil is noted, and it is not formulated for pediatric use.

**Docetaxel** is another experimental medication used in this trial. It is available as a concentrate for solution for infusion and is administered intravenously. The maximum daily dose is 50 mg/m², with a total maximum dose of 400 mg/m² over the same treatment period of 33 days. Like Fluorouracil, Docetaxel is of chemical origin and is not a pediatric formulation.

The trial also includes **Oxaliplatin**, which is provided as a solution for injection. This medication is administered intravenously, with a maximum daily dose of 85 mg/m² and a total maximum dose of 735 mg/m² over 33 days. Oxaliplatin is chemically derived and is not intended for pediatric use.

Lastly, **Calcium Folinate** is used in the study as a solution for injection or infusion. It is administered intravenously, with a maximum daily dose of 200 mg/m² and a total maximum dose of 1600 mg/m² over the 33-day treatment period. Calcium Folinate is also of chemical origin and is not formulated for pediatric patients.

All medications are administered intravenously, and the trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of the clinical trial will be assessed primarily through the evaluation of **progression-free survival (PFS)** in patients with resectable adenocarcinoma of the gastroesophageal junction (GEJ). This primary endpoint aims to determine whether the addition of preoperative radiochemotherapy is superior to perioperative chemotherapy alone in improving PFS for patients undergoing oncologically adequate surgery, including D2 resection and appropriate mediastinal lymphadenectomy.

Secondary endpoints will include overall survival, with specific attention to survival rates at 1, 3, and 5 years, as well as the R0 resection rate, which indicates the completeness of tumor removal. Additional parameters will involve the number of harvested lymph nodes, the site of tumor relapse, and perioperative morbidity and mortality rates. Safety and toxicity will be assessed according to the NCI CTC criteria. Quality of life will be evaluated using the EORTC QLQ-C30 and the esophagogastric module OG25.