Evaluation of Neo-Adjuvant Chemotherapy with FOLFOX Regimen in Elderly Patients with Locally Advanced Resectable Colon Carcinoma

The primary objective of the study is to demonstrate that the proportion of patients with **colon carcinoma** who are alive and disease-free at 3 years post-randomization is superior in those treated with 6 weeks (3 courses) of NeoAdjuvant Chemotherapy (FOLFOX) followed by surgery, compared to those who proceed directly to surgery. This objective is clinically relevant as it aims to establish a more effective treatment protocol for improving long-term survival and disease-free status in elderly patients with locally advanced but resectable colon cancer.

Secondary objectives include evaluating:

• Tumour regression grade and score on the surgical sample at the time of surgery
• Histopathological endpoints on the surgical sample
• Short-term efficacy and its association with longer-term outcomes, such as recurrence within 1 year after surgery and downstaging post-NeoAdjuvant Chemotherapy
• Safety and toxicity
• Cancer-specific survival and overall survival
• Surgical morbidity and mortality
• Patient-reported outcomes
• Geriatric assessment scoring
• Medium and long-term efficacy

The clinical trial involves a total of **609 participants** diagnosed with **colon carcinoma**. The study population includes both male and female subjects, with an age range starting from 70 years and above. Participants were selected based on specific criteria, including biopsy-confirmed adenocarcinoma of the colon, adequate renal and hepatobiliary function, and eligibility for curative surgery. The trial does not include a vulnerable population. Participants are required to have a radiological stage of T3/T4 and N0/N1/N2 and M0, and must be assessed as fit to receive 6 weeks of NeoAdjuvant Chemotherapy (FOLFOX) followed by surgery. Lifestyle factors such as diet and physical activity are not specified in the trial data provided. The selection process ensures that participants are able to understand and provide informed consent, and are affiliated with a social security scheme.

The clinical trial is designed to evaluate the efficacy of **neoadjuvant chemotherapy** in patients aged 70 years or older with locally advanced but resectable **colon carcinoma**. This is a randomized, controlled, and double-blind study, aiming to compare the outcomes of patients receiving 6 weeks (3 courses) of neoadjuvant chemotherapy (FOLFOX regimen) followed by surgery, against those undergoing immediate surgery. The primary endpoint is disease-free survival, defined as the time from randomization to the first event of recurrence, treatment failure, or death from any cause. Secondary endpoints include histopathological evaluation, short-term efficacy, safety and toxicity, overall and cancer-specific survival, surgical morbidity, post-operative mortality, and quality of life assessments.

The trial is expected to last until September 2031, with recruitment starting in September 2023. Participants will be involved in the study for a maximum of 6 months, corresponding to the treatment period. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits during the treatment phase to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. Inclusion criteria require participants to have biopsy-confirmed adenocarcinoma of the colon, adequate renal and hepatobiliary function, and be eligible for curative surgery, among other conditions. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or withdraw consent. The trial will utilize **folinic acid**, **fluorouracil**, and **oxaliplatin** as part of the chemotherapy regimen, administered intravenously. The study aims to refine and personalize treatment strategies for elderly patients with colon cancer, potentially improving survival outcomes and quality of life.

The clinical trial involves the administration of several **chemotherapy** agents, each with specific dosing and administration protocols. **Folinic Acid** is provided as a **solution for injection** and is administered intravenously. The maximum daily dose is 400 mg/m², with a total maximum dose of 1200 mg/m² over a treatment period of up to 6 weeks. This agent is used in conjunction with other chemotherapy drugs to enhance their efficacy and reduce toxicity.

**Fluorouracil** is utilized in two different forms: as a **solution for injection/infusion** and as a **solution for intravenous bolus use**. For the infusion form, the maximum daily dose is 2400 mg/m², with a total maximum dose of 7200 mg/m² over the same 6-week period. The bolus form has a maximum daily dose of 400 mg/m² and a total maximum dose of 1200 mg/m². Both forms are administered intravenously and are integral components of the chemotherapy regimen, targeting rapidly dividing cancer cells.

**Oxaliplatin** is administered as a **powder and solvent for solution for infusion**. It is given intravenously with a maximum daily dose of 85 mg/m² and a total maximum dose of 255 mg/m² over the 6-week treatment period. Oxaliplatin is a platinum-based drug that works by causing DNA crosslinking and subsequent apoptosis of cancer cells.

All medications are administered as part of a **neo-adjuvant chemotherapy** regimen, specifically the FOLFOX protocol, which is designed to treat locally advanced but resectable colon cancer in elderly patients aged 70 years or older. The trial aims to assess the efficacy of this regimen in improving survival and disease-free outcomes compared to immediate surgical intervention. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy in the clinical trial will be assessed primarily through the measurement of **disease-free survival (DFS)**. DFS is defined as the time from randomization to the first event, which may include a first recurrence, either local or metastatic, treatment failure, or death from any cause. This primary endpoint will provide a direct measure of the treatment's effectiveness in prolonging the period during which patients remain free from disease.

Secondary endpoints will include a comprehensive histopathological evaluation, assessing criteria such as tumor cell density, maximum tumor size, depth of invasion, and lymph node involvement. Short-term efficacy will be evaluated by assessing disease stage reduction following neoadjuvant chemotherapy within one year after surgery. Safety and toxicity will be monitored according to treatment-related toxicities using the NCI-CTCAE version 5.0. Overall and cancer-specific survival will be tracked from the date of randomization to the date of death from any cause or cancer-specific causes, respectively.

Additional assessments will include the rate of surgical morbidity, defined by the percentage of complications according to the Clavien-Dindo classification, and post-operative mortality, defined as any death within 90 days after surgery or during the hospital stay. Quality of life will be evaluated using the cancer-specific QLQ-C30 and colon cancer-specific QLQ-CR29 questionnaires, along with the EQ-5D-5L questionnaire. A geriatric assessment will be conducted using tools such as the G8, IADL, ADL, and functional domain questionnaires, at baseline, within 12 weeks following surgery, at 1 year, and 3 years post-surgery.