Phase III Randomized Study of Adjuvant Chemotherapy with Levoleucovorin, Capecitabine, Folinic Acid, and Fluorouracil in Resected Stage III Colon Adenocarcinoma in Patients Aged 70+

The primary objective of the PRODIGE 34 - ADAGE study is to compare the **relapse-free survival** (RFS) at 3 years for two therapeutic strategies in patients aged 70 and over following resection of stage III colon adenocarcinoma. This objective is clinically relevant as it aims to determine the most effective adjuvant chemotherapy regimen for improving long-term outcomes in an older population, which is often underrepresented in clinical trials. The study focuses on evaluating the efficacy of adjuvant chemotherapy in enhancing survival rates and reducing the risk of cancer recurrence in this specific age group.

The clinical trial focuses on patients diagnosed with **colon cancer**, specifically targeting individuals aged 70 and over who have undergone a stage III upper rectal or colon cancer resection. The study population includes both male and female participants, with no vulnerable populations selected. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including the ability to start adjuvant chemotherapy within 12 weeks post-surgery and having no prior chemotherapy for colon cancer. Lifestyle considerations such as effective contraception for male patients during and after treatment are noted. The trial aims to compare the relapse-free survival at 3 years for two therapeutic strategies in this demographic.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy of adjuvant **chemotherapy** in patients aged 70 and older who have undergone resection for stage III colon adenocarcinoma. The primary objective is to compare the **relapse-free survival** (RFS) at three years between two therapeutic strategies. The trial is expected to run until August 31, 2025, with recruitment having commenced on January 25, 2015. Participants will be involved in the study for a maximum treatment period of six months, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥70 years), effective contraception for male patients, and the ability to start adjuvant chemotherapy within 12 weeks post-surgery. Following the screening, participants will undergo regular follow-up visits to monitor treatment tolerance, dose intensity, and overall survival. The end-of-study visit will assess the primary endpoint of RFS and secondary endpoints, including overall tolerance, time to recurrence, and quality of life metrics.

Participants will receive one of the following investigational products: **levoleucovorin**, **capecitabine**, **folinic acid**, or **fluorouracil**, administered either orally or via **intravenous perfusion**. The study will ensure that all products are administered according to their respective maximum daily and total dose amounts. The trial's design and procedures are structured to maintain scientific rigor and ensure the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **ELVORINE** 100 mg/10 mL, a **solution for injection** containing the active substance **levoleucovorin**. This pharmaceutical form is intended for **intravenous perfusion use**. The maximum daily dose is 85 mg/m², with a total dose not exceeding 85 mg/m² over a treatment period of up to 6 months. The product is manufactured by Pfizer Holding France and is used in conjunction with chemotherapy. Participant compliance is monitored through regular assessments of dosing schedules and administration records.

**Xeloda** 150 mg film-coated tablets, containing the active substance **capecitabine**, are administered orally. The maximum daily dose is 1000 mg/m², with a total dose not exceeding 1000 mg/m² over a 6-month treatment period. This product is manufactured by Cheplapharm Arzneimittel GmbH and is also used in combination with chemotherapy. Compliance is ensured by tracking pill counts and patient diaries.

**Folinic acid** (as calcium folinate) 10 mg/mL solution for injection/infusion is another treatment used in the trial. This product, manufactured by Kalceks, is administered via **intravenous perfusion use**. The maximum daily dose is 400 mg/m², with a total dose not exceeding 400 mg/m² over a 6-month period. It is used alongside chemotherapy, and compliance is monitored through infusion records and patient follow-ups.

**FLUOROURACILE TEVA** 1000 mg/20 mL, a solution for injection, contains the active substance **fluorouracil**. This product is administered through **intravenous perfusion use**. The maximum daily dose is 400 mg/m², with a total dose not exceeding 400 mg/m² over a 6-month treatment period. Manufactured by Teva Santé, it is used in combination with chemotherapy. Compliance is tracked through infusion logs and regular patient assessments.

Efficacy in the clinical trial will be assessed primarily through the measurement of **relapse-free survival (RFS)**. This primary endpoint is defined as the duration from the date of randomization to the date of the first recurrence, either local or remote, or the date of death from any cause. Patients who are alive without recurrence will be censored at the date of their last assessment. Secondary endpoints include the dose intensity, overall tolerance to the treatments, time to recurrence, overall survival, time to decrease in autonomy, and time to decrease in quality of life. These parameters will be collected and analyzed to provide a comprehensive evaluation of the treatment's efficacy. The trial aims to compare these outcomes for two therapeutic strategies in patients aged 70 and over following resection of stage III upper rectal or colon cancer. The assessments will be conducted at specified intervals throughout the trial to ensure accurate and reliable data collection.