Aspirin Trial

Rationale: Preclinical, epidemiologic and clinical evidence suggest that acetylsalicylic acid use may reduce overall cancer risk and mortality in colon cancer patients.



Objective: To investigate acetylsalicylic acid 80 mg po daily for 5 years as an adjuvant therapy in curatively operated, stage II and III colon cancer patients.



Study design: A phase III double-blind placebo-controlled randomised trial of adjuvant low-dose acetylsalicylic acid in colon cancer patients. The question will be addressed by means of two parallel studies in patients treated with or without adjuvant chemotherapy.



Inclusion criteria

1. Histologically confirmed adenocarcinoma of the colon

2. TNM stage: pT3-4; N0-2 and M0, or pT1-2 and N1-2 (UICC stage II and III) (in case of >1 tumour: largest tumour is stage II or III)

3. Age ≥ 45 years

4. Completed surgical resection (R0) within 12 weeks of randomisation

5. Written informed consent according to local Ethics Committee requirements

Exclusion criteria

1. Rectal cancer (defined as tumor within 15 cm from the anal verge)

2. Currently taking oral anti-coagulants.

3. Currently taking (low-dose) aspirin for any reason

4. History of bleeding disorders or active gastric or duodenal ulcers

5. Currently taking high dose (≥ 30 mg predniso(lo)ne) systemic glucocorticoids

6. Patients with (suspected) (non-) polyposis syndrome (FAP/AFAP, MAP, Lynch
syndrome)

7. Patients with >100 polyps of the colon or a known hereditary syndrome of the colon in a
first degree family member

8. Local or distant recurrent disease

9. Allergy or intolerance for salicylates

10. History of other malignancies in the last 5 years, except for SSC, BCC or CIN

11. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule

Intervention: Patients will be randomised for acetylsalicylic acid 80 mg po daily for 5 years versus placebo.



Main study parameters/endpoints: The primary endpoint of the trial is 5 year Overall Survival (5-yr OS). Secondary endpoints are Time to Treatment Failure (TTF; time elapsed between randomisation until treatment discontinuation due to disease recurrence, unacceptable toxicity, death or any other event of interest) and 3-year Disease Free Survival (DFS); time to recurrence or death due to any cause. The trial is powered to identify a hazard ratio of 0.75 in the acetylsalicylic acid arm, with 80 percent power and a type 1 error of 0.05 (2-sided). In order for the trial to be successful, 1588 patients need to be randomised.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Unexpected adverse events may occur. Given the widespread use of low dose acetylsalicylic acid in cardiovascular risk management, it is unlikely that new toxicities will be identified. However, adverse anti-cancer effects may be identified. An independent data safety monitoring board will oversee trial conduct. A planned interim futility analysis allows early termination of the study if it appears that acetylsalicylic acid will not favourably impact colon cancer outcome.

Preclinical, epidemiologic and clinical evidence suggest that aspirin use may reduce overall cancer risk and mortality in colon cancer patients.

1. Inclusion: 3 years;

2. Follow-up 5 years;

3. Total years: 8.

Aspirin 80 mg once daily during 5 years or placebo after surgery.

Follow-up of the colon cancer according to national guidelines, no additional visits or interventions besides aspirin or placebo.