A Phase III double-blind placebo-controlled Randomised Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients

The primary objective of this Phase III double-blind, placebo-controlled randomized trial is to evaluate the effect of **acetylsalicylic acid** (80 mg orally once daily for 5 years) on 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 this patient population, potentially offering a simple and cost-effective adjunctive treatment option.

Secondary objectives include:

• Assessing the effect of acetylsalicylic acid on 3-year disease-free survival (DFS), which is important for understanding its impact on recurrence rates.
• Evaluating the effect on time to treatment failure (TTF), providing insights into the duration of treatment efficacy.
• Investigating the effect on toxicity, including interactions with chemotherapy, to ensure patient safety and optimize treatment regimens.

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. Participants must have undergone curative radical resection (R0 resection) within 12 weeks prior to study entry and have a TNM stage of pT3-4; N0-2 and M0, or pT1-2 and N1-2, corresponding to UICC stage II and III, according to TNM version 7. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to provide written informed consent in accordance with national and local regulations. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial aims to evaluate the effect of 80mg acetylsalicylic acid, administered orally once daily for five years, on the five-year overall survival of stage II and III colon cancer patients.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled study to evaluate the effect of **acetylsalicylic acid** on recurrence and survival in patients with resected colon carcinoma. The trial aims to assess the impact of administering 80 mg of acetylsalicylic acid orally once daily over a period of five years on the five-year overall survival (OS) of patients with stage II and III colon cancer. The study is expected to conclude by December 31, 2027, with recruitment having commenced on September 1, 2014.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (45 years and older), histologically confirmed adenocarcinoma of the colon, and specific TNM staging. Following the screening, eligible participants will be randomized to receive either acetylsalicylic acid or a placebo. The trial includes regular follow-up visits to monitor the participants' health status, adherence to the treatment regimen, and to collect data on primary and secondary endpoints, including disease-free survival (DFS) and time to treatment failure (TTF). The end-of-study visit will occur at the conclusion of the five-year treatment period or upon early termination.

The expected length of participant involvement is five years, with conditions for early termination including withdrawal of consent, adverse events, or any medical condition that contraindicates continued participation. The trial's primary endpoint is the five-year overall survival, with secondary endpoints focusing on disease-free survival and time to treatment failure. The study is conducted under strict adherence to ethical guidelines, ensuring that all participants provide written informed consent according to national and local regulations.

The clinical trial involves the administration of **acetylsalicylic acid**, commonly known as aspirin, as the experimental medication. The pharmaceutical form of this medication is a tablet, and it is administered orally. The dosage is set at 80 mg, with a frequency of once daily. The treatment period is designed to last for a maximum of 60 months. The primary objective of this trial is to evaluate the effect of acetylsalicylic acid on the five-year overall survival of patients with stage II and III colon cancer. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this double-blind, placebo-controlled trial. The placebo is also in tablet form and is administered orally at a dosage of 80 mg once daily, mirroring the administration schedule of the acetylsalicylic acid. The use of a placebo allows for the assessment of the true efficacy of the experimental medication by providing a control group for comparison. Participant compliance with the placebo regimen will be similarly monitored to maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed using the primary endpoint of 5-year **Overall Survival (OS)** for patients with stage II and III colon cancer. Secondary endpoints include **Disease Free Survival (DFS)** and **Time to Treatment Failure (TTF)**. The trial is designed to evaluate the effect of 80 mg of acetylsalicylic acid, administered orally once daily, on these endpoints over a 5-year period. Data collection will occur at specified intervals throughout the trial duration, with final analysis conducted at the end of the treatment period. The trial employs a double-blind, placebo-controlled methodology to ensure unbiased results. The efficacy parameters will be measured and analyzed using validated clinical scales and statistical methods appropriate for survival analysis. The trial aims to provide robust data on the potential benefits of acetylsalicylic acid in improving survival outcomes for colon cancer patients.