Evaluation of Neoadjuvant Chemotherapy with Oxaliplatin and Capecitabine in Locally Advanced Colon Cancer Patients

The primary objective of this study is to determine if the proposed treatment regimen, which includes **neoadjuvant chemotherapy**, surgery, and complementary chemotherapy, enhances **Disease-Free Survival (DFS)** at 2 years postoperatively in patients with **locally advanced colon cancer (LACC)**, compared to the standard treatment of surgery and complementary chemotherapy. This is clinically relevant as improving DFS can potentially lead to better long-term outcomes and quality of life for patients with LACC.

Secondary objectives include:

• Evaluating whether the treatment increases DFS at 5 years postoperatively compared to the standard treatment.
• Assessing whether the treatment increases **Overall Survival (OS)** at 2 and 5 years postoperatively compared to the standard treatment.
• Comparing postoperative morbidity and mortality between the neoadjuvant treatment and standard treatment.
• Analyzing the toxicity in each treatment group.
• Analyzing the degree of therapeutic completion in each group.
• Assessing the accuracy of **CT** in diagnosing LACC in the control group.
• Evaluating the ability of CT to quantify the degree of tumor response after neoadjuvant treatment in the intervention group.
• Validating the usefulness of scales used for assessing pathological tumor response in rectal cancer for determining response in colon cancer after neoadjuvant treatment.
• Comparing the impact of adding **oxaliplatin** on the pathological response in patients over 70 years receiving neoadjuvant chemotherapy.

The clinical trial focuses on individuals diagnosed with **locally advanced colon cancer (LACC)**. The study population includes both male and female participants aged over 18 years, with a good general health status as indicated by a Karnofsky score greater than 60% or an ECOG score less than 2. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including histological confirmation of colon adenocarcinoma and radiologically resectable disease, with the intent to undergo elective surgery with curative intent. The trial requires participants to have adequate hematological and renal function, as well as the absence of contraindications for chemotherapy. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effectiveness of **neoadjuvant chemotherapy** in the treatment of **locally advanced colon cancer**. This study is a randomized, double-blind, controlled trial, categorized as a low-intervention Phase 4 trial. The primary objective is to determine if the proposed treatment regimen, which includes neoadjuvant chemotherapy, surgery, and complementary chemotherapy, enhances disease-free survival at two years postoperatively compared to the standard treatment of surgery followed by complementary chemotherapy. The trial is expected to conclude by July 31, 2029, with recruitment having commenced on March 10, 2017.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histological confirmation of colon adenocarcinoma, radiologically resectable disease, and a good general condition (Karnofsky >60% or ECOG <2). The inclusion visit will also involve laboratory assessments to ensure adequate hemoglobin, leukocyte, platelet levels, and renal function, alongside the absence of contraindications for chemotherapy. Following the inclusion visit, participants will receive treatment with **oxaliplatin** and **capecitabine**, administered intravenously and orally, respectively, over a maximum treatment period of nine months.

Subsequent follow-up visits will monitor the participants' response to treatment, assess any adverse events using the CTCAE scale, and evaluate the degree of therapeutic completion. The primary endpoint is the two-year disease-free survival, while secondary endpoints include five-year disease-free and overall survival, postoperative morbidity and mortality, and the presence of local or distant recurrence. The study will also assess the accuracy of CT imaging in diagnosing locally advanced colon cancer and the utility of pathological tumor response scales.

The expected length of participant involvement is up to nine months, with conditions for early termination including the development of contraindications for chemotherapy, significant adverse events, or withdrawal of consent. The end-of-study visit will involve a comprehensive evaluation of the treatment outcomes and any long-term effects. This trial aims to provide valuable insights into the potential benefits of neoadjuvant chemotherapy in improving survival outcomes for patients with locally advanced colon cancer.

The clinical trial involves the administration of **Oxaliplatin**, marketed as Oxaliplatin Hospira 5 mg/ml concentrate for solution for infusion. This experimental medication is provided in the form of a concentrate for solution for infusion, intended for **intravenous** administration. The dosing regimen specifies a maximum daily dose of 130 mg/m², with a total maximum dose of 390 mg/m² over a treatment period of up to 9 weeks. The active substance, oxaliplatin, is of chemical origin and is classified under the ATC code L01XA03. The product is manufactured by Hospira UK Limited, Walton Oaks, and is not a paediatric formulation.

Another experimental medication used in the trial is **Capecitabine**, available as Capecitabine Accord 150 mg film-coated tablets. This medication is administered **orally** and is also of chemical origin. The dosing schedule allows for a maximum daily dose of 1000 mg/m², with a cumulative maximum dose of 42000 mg/m² over a 9-week treatment period. Capecitabine is classified under the ATC code L01BC06 and is produced by Accord Healthcare S.L.U. Similar to oxaliplatin, this formulation is not intended for paediatric use.

Both medications are utilized in the context of evaluating the effectiveness of neoadjuvant chemotherapy in the treatment of locally advanced colon cancer. The trial aims to assess whether the combination of these treatments, followed by surgery and complementary chemotherapy, enhances Disease-Free Survival (DFS) at 2 years postoperatively compared to the standard treatment regimen. Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment protocols.

The efficacy of the neoadjuvant chemotherapy treatment in the clinical trial for locally advanced colon cancer will be assessed primarily through the measurement of **Disease-Free Survival (DFS)** at 2 years postoperatively. This primary endpoint aims to determine the effectiveness of the treatment regimen, which includes neoadjuvant chemotherapy, surgery, and complementary chemotherapy, compared to the standard treatment of surgery and complementary chemotherapy alone.

Secondary endpoints will include DFS and overall survival (OS) at 5 years after randomization, as well as postoperative morbidity and mortality, which will be evaluated by the frequency and type of postoperative complications and transfusion requirements. The presence of local or distant recurrence and its location will also be assessed. Toxicity will be measured according to the CTCAE scale version 4.0. The degree of therapeutic completion in each group will be analyzed, along with the accuracy of CT scans in diagnosing locally advanced colon cancer (LACC) in the control group by correlating preoperative CT staging with pathological analysis.

Additional assessments will include the information provided by restaging CT scans regarding the degree of regression at the pathological level, with calculations of sensitivity, specificity, and positive/negative predictive values. The utility of scales commonly used in assessing pathological tumor response in rectal cancer will be evaluated for their applicability in colon cancer after neoadjuvant treatment. In patients over 70 years of age receiving neoadjuvant chemotherapy, the impact of adding **oxaliplatin** on the pathological response will be examined.