Phase III Randomized Double‑Blind Placebo‑Controlled Trial of Low‑Dose Acetylsalicylic Acid for Recurrence and Overall Survival in Resected Stage II–III Colon Cancer

The primary objective of this Phase III double-blind, placebo-controlled randomized trial is to evaluate the effect of 80 mg **acetylsalicylic acid** administered orally once daily for five years on the 5-year overall survival (OS) in patients with stage II and III colon cancer. This objective is clinically relevant as it aims to determine whether acetylsalicylic acid can improve survival outcomes in patients who have undergone resection for colon carcinoma, potentially offering a simple and cost-effective adjuvant therapy option.

Secondary objectives include:

• To study the effect of acetylsalicylic acid on 3-year disease-free survival (DFS).
• To study the effect of acetylsalicylic acid on time to treatment failure (TTF).
• To study the effect of acetylsalicylic acid on toxicity, including its interaction with chemotherapy.

The clinical trial involves **patients with resected colon carcinoma**, specifically targeting individuals with histologically confirmed adenocarcinoma of the colon. The study population includes both male and female participants aged 45 years and older, who have undergone curative radical resection (R0 resection) within 12 weeks prior to study entry. Participants must have a TNM stage of pT3-4; N0-2 and M0, or pT1-2 and N1-2, corresponding to UICC stage II and III. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of individuals who have provided written informed consent according to national and local regulations. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase III double-blind, placebo-controlled, randomized trial** designed to evaluate the effect of **acetylsalicylic acid** on recurrence and survival in patients with resected colon carcinoma. The primary objective is to assess the impact of 80 mg of acetylsalicylic acid, administered orally once daily, on the five-year overall survival (OS) of patients with stage II and III colon cancer. The trial is expected to run from January 10, 2018, to December 31, 2027, with a maximum treatment period of 60 months for each participant.

Participants will be randomly assigned to receive either acetylsalicylic acid or a **placebo**. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor health status and treatment adherence, and an end-of-study visit to collect final data. The inclusion criteria specify that participants must be 45 years or older, have histologically confirmed adenocarcinoma of the colon, and have undergone curative radical resection within 12 weeks prior to study entry. Written informed consent is required according to national and local regulations.

The primary endpoint is the five-year overall survival, defined as the time from randomization to death from any cause. Secondary endpoints include disease-free survival, which measures the time to disease recurrence or death, and time to treatment failure, which considers treatment discontinuation due to disease progression, unacceptable toxicity, or death. Participants are expected to be involved in the study for up to five years, with conditions for early termination including disease progression, adverse events, or withdrawal of consent.

The clinical trial involves the administration of **acetylsalicylic acid** as the experimental medication. This compound is provided in the form of a **tablet** and is administered orally. The dosage is set at 80 mg per day, with a maximum total dose of 146 g over the course of the study. The treatment period is defined as 60 months, during which participants will receive the medication once daily. The primary objective is to evaluate the effect of acetylsalicylic acid on the overall survival of patients with stage II and III colon cancer. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a control. The placebo is identical in pharmaceutical form to the experimental medication, being a **tablet** administered orally. The placebo contains no active pharmaceutical ingredients and is chemically inert. Participants in the placebo group will follow the same administration schedule as those receiving acetylsalicylic acid, with daily oral administration for a period of 60 months. This design allows for a double-blind comparison to assess the efficacy of the experimental treatment. Monitoring of participant compliance will be conducted to maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed primarily through the measurement of **Overall Survival (OS)** over a five-year period. The primary endpoint is defined as the time interval between the date of randomization and the date of death. Patients who are alive at the last follow-up date will be censored for analysis, with the time at risk corresponding to the interval from randomization to the last follow-up date.

Secondary endpoints include **Disease-Free Survival (DFS)** and **Time to Treatment Failure (TTF)**. DFS is defined as the time from randomization to either disease recurrence or death, whichever occurs first. Recurrence can be loco-regional, distant, or a new primary colon cancer, with documentation required in the patient's file. The date of radiological evidence or colonoscopy will be considered the date of recurrence. TTF measures the time from randomization until treatment discontinuation due to disease progression, unacceptable toxicity, death, or any other event of interest.