Evaluation of Capecitabine and Oxaliplatin in Neoadjuvant and Adjuvant Therapy for High-Risk Rectal Cancer to Mitigate Metastatic Recurrence

The primary objective of the study titled "Systemic Neoadjuvant and adjuvant Control by Precision medicine in **rectal cancer** (SYNCOPE) – approach on high-risk group to reduce metastases" is to evaluate the feasibility of applying a systemic control with a precision approach throughout the course of rectal cancer therapy. This approach aims to improve recurrence-free survival in patients with rectal cancer. The clinical relevance of this objective lies in its potential to enhance treatment outcomes and reduce the risk of metastases in high-risk patient groups, thereby improving overall patient prognosis.

The clinical trial focuses on patients diagnosed with **rectal cancer**, specifically targeting individuals with rectal adenocarcinoma. The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants are required to have a WHO performance status of 0-1, indicating they are in relatively good health and capable of self-care. The trial does not include vulnerable populations. The selection criteria necessitate that participants are assessed by a multidisciplinary team (MDT) to be suitable for CAPOX (capecitabine and oxaliplatin) treatment and require either radiotherapy (RT) or chemoradiotherapy (CRT) based on current standards. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is designed to evaluate the efficacy of a **systemic control** with a precision approach in the treatment of **rectal cancer**. This study is a randomized, double-blind, controlled trial, aiming to improve recurrence-free survival in patients with rectal adenocarcinoma. The trial will involve the administration of **capecitabine** and **oxaliplatin** as part of the CAPOX regimen, with capecitabine administered orally and oxaliplatin via intravenous infusion. The trial is expected to run from July 2021 to December 2026, with a primary endpoint of recurrence-free survival at three and five years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as WHO performance status 0-1 and the requirement for radiotherapy (RT) or chemoradiotherapy (CRT) as determined by a multidisciplinary team (MDT). Follow-up visits will be scheduled to monitor treatment response and manage any adverse effects. The end-of-study visit will evaluate the overall treatment outcomes and collect final data for analysis. The expected length of participant involvement is up to 12 months, depending on individual treatment response and tolerance.

Conditions that may lead to early termination from the study include significant adverse reactions to the treatment, disease progression, or withdrawal of consent by the participant. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **Capecitabine**, marketed as Capecitabine Orion 150 mg film-coated tablets. This experimental medication is administered orally. The dosage is calculated based on body surface area, with a maximum daily dose of 2000 mg/m² and a total maximum dose of 56000 mg/m² over a treatment period of up to 12 weeks. Capecitabine is a cytotoxic chemotherapy agent, and its administration is monitored to ensure participant compliance with the dosing schedule.

Another experimental medication used in the trial is **Oxaliplatin**, available as Oxaliplatin Accord 5 mg/ml solution for infusion. This medication is administered via intravenous infusion. The dosage is also based on body surface area, with a maximum daily dose of 85 mg/m² and a total maximum dose of 340 mg/m² over a treatment period of up to 10 weeks. Oxaliplatin, like Capecitabine, is a cytotoxic chemotherapy agent, and its administration is carefully monitored to ensure adherence to the prescribed dosing regimen.

Both medications are part of a systemic neoadjuvant and adjuvant control strategy aimed at improving recurrence-free survival in patients with rectal cancer. The trial does not include any non-experimental treatments such as placebo or comparator treatments. Compliance with the treatment protocol is essential, and participant adherence is closely monitored throughout the study duration.

Efficacy in the clinical trial titled "Systemic Neoadjuvant and adjuvant Control by Precision medicine in rectal cancer (SYNCOPE) – approach on high-risk group to reduce metastases" will be assessed primarily through the endpoint of **recurrence-free survival** at 3 and 5 years, evaluated using an intention-to-treat analysis. This endpoint is designed to measure the effectiveness of the treatment strategy in improving the survival of patients with rectal cancer without the recurrence of the disease. The trial involves the administration of a combination therapy of **capecitabine** and **oxaliplatin** (CAPOX), which are cytotoxic chemotherapeutic agents. The treatment period for capecitabine is up to 12 weeks, while oxaliplatin is administered for a maximum of 10 weeks. The trial aims to apply a systemic control with a precision approach to enhance the treatment strategy and improve patient outcomes. The efficacy assessments will be conducted at specified intervals to monitor the recurrence-free survival rates over the designated timeframes.