Phase II Randomized Trial of Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin, and Drug Combination in Locally Advanced Rectal Cancer

The primary objective of this randomized phase II trial is to compare the long-term and short-term outcomes in patients with **rectal cancer** undergoing standard treatment, which includes radio-chemotherapy followed by surgery, versus an experimental approach involving neoadjuvant chemotherapy followed by surgery. This comparison is clinically relevant as it may provide insights into optimizing treatment strategies for locally advanced rectal cancer, potentially improving patient outcomes and reducing treatment-related morbidity.

Secondary objectives include evaluating whether early surgical and medical complications, functional outcomes, toxicity, and quality of life (QoL) can be improved by avoiding radiotherapy. Additionally, exploratory analyses are planned to identify potential predictive markers that could guide the selection of patients for either radio-chemotherapy/surgery or neoadjuvant combination chemotherapy/surgery. These objectives aim to enhance personalized treatment approaches and improve overall patient care in rectal cancer management.

The clinical trial involves participants diagnosed with **rectum cancer**, specifically adenocarcinoma of the rectum. The study population includes both male and female subjects, aged 18 years and older, with no vulnerable populations selected. Participants are required to have a locally advanced tumor, as determined by imaging, and must be deemed resectable at a multidisciplinary team conference. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate bone marrow, liver, and renal function to undergo systemic chemotherapy. Lifestyle considerations include the use of contraception for fertile women and male patients with a fertile partner. The trial population was selected based on these criteria, ensuring that participants are suitable for either standard treatment or experimental neoadjuvant chemotherapy followed by surgery.

The clinical trial is designed to evaluate the efficacy and safety of neoadjuvant chemotherapy compared to standard treatment in patients with **rectum cancer**. This is a randomized, phase II trial with a double-blind, controlled design. The trial aims to assess both long-term and short-term outcomes in patients undergoing either standard treatment, which includes radio-chemotherapy followed by surgery, or an experimental approach involving neoadjuvant chemotherapy followed by surgery. The primary endpoint is disease-free survival, while secondary endpoints include overall survival, local and distant relapse, early and late toxicity, functional outcomes, quality of life, resection rate, postoperative morbidity and mortality, rate of downsizing, tumor regression grade, and translational research.

The trial is expected to run from March 1, 2017, to December 31, 2030. Participants will be involved in the study for the duration of their treatment and follow-up, which may vary depending on individual response and treatment schedules. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and side effects, and an end-of-study visit to assess final outcomes. Participants must meet specific inclusion criteria, such as having adenocarcinoma of the rectum, being deemed resectable, and having adequate organ function. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent.

The investigational products used in the trial include **capecitabine**, **oxaliplatin**, **fluorouracil**, and **calcium folinate pentahydrate**, administered either orally or intravenously, depending on the specific treatment regimen. The trial is categorized as low intervention, focusing on comparing the efficacy and safety of the treatment modalities. Participants are required to provide written and oral informed consent before enrollment, and the study adheres to ethical guidelines to ensure participant safety and data integrity.

The clinical trial involves the administration of several **experimental medications** and comparator treatments for the management of locally advanced rectal cancer. The primary experimental medication is **Capecitabine**, which is administered in various formulations. **Capecitabine Pharmacare** is provided as 150 mg film-coated tablets for oral use. The dosage and frequency of administration are determined based on the trial protocol, ensuring adherence to the specified treatment regimen. **Capecitabine Glenmark** is available in two dosages: 150 mg and 500 mg film-coated tablets, also administered orally. Similarly, **Capecitabine Accord** is provided as 500 mg film-coated tablets for oral administration. All formulations of Capecitabine are chemically derived and are not pediatric formulations.

In addition to Capecitabine, the trial includes the administration of **Oxaliplatin**, which is provided as a 5 mg/ml concentrate for solution for infusion. This medication is administered intravenously, with the dosage and infusion schedule tailored to the trial's requirements. Oxaliplatin is a chemically synthesized compound and is not intended for pediatric use.

The trial also incorporates **Fluorouracil**, available as a 50 mg/ml solution for injection. This medication is administered intravenously, with dosing schedules aligned with the trial protocol. Fluorouracil is a chemical compound and is not formulated for pediatric patients.

**Leucovorin**, in the form of a 10 mg/ml solution for injection or infusion, is used as a supportive treatment. It is administered intravenously, with the dosing regimen designed to complement the primary chemotherapy agents. Leucovorin is chemically derived and is not a pediatric formulation.

Participant compliance with the medication regimen is monitored throughout the trial to ensure adherence to the prescribed dosing schedules. The trial protocol outlines specific measures for compliance monitoring, including regular assessments and documentation of medication intake. The trial aims to evaluate the efficacy and safety of these treatments in comparison to standard care, with outcomes measured over both short and long-term periods.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is **disease-free survival**, which will be measured to evaluate the effectiveness of the treatment in preventing the recurrence of rectal cancer. Secondary endpoints include overall survival, local and distant relapse, early and late toxicity, functional outcome and quality of life (QoL), resection rate, postoperative morbidity and mortality, rate of downsizing, tumor regression grade, and translational research. These parameters will provide a comprehensive assessment of the treatment's impact on patients.

The collection and analysis of these efficacy parameters will be conducted at various timepoints throughout the trial. The trial aims to compare long-term and short-term outcomes in patients undergoing standard treatment (radio-chemotherapy/surgery) versus experimental neoadjuvant chemotherapy/surgery. The study is designed to ensure that all relevant data is systematically gathered and analyzed to determine the efficacy of the treatment regimens being tested.