ASPIRIN

A phase III double-blind placebo-controlled randomised trial is proposed. Stage II and III colon cancer patients with or without adjuvant chemotherapy will be randomised between low-dose acetylsalicylic acid (80 mg) or placebo, within 12 weeks after radical resection. Treatment will start at least 10 days after surgery. Study medication will be continued for 5 years. The research question will be addressed in patients with and without adjuvant chemotherapy by means of two parallel studies.

Primary Objective:
• To study the effect of 80mg acetylsalicylic acid (given orally once daily for 5 years) on 5 year overall survival (OS) for stage II and III colon cancer patients
Secondary Objective(s):
• 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, for example the interaction of acetylsalicylic acid with chemotherapy
Tertiary Objective (s):
• Genetic analysis on surgical specimen from all patients: PIK3CA, BRAF and RAS mutation analysis
•  Evaluation of therapeutic compliance (using a diary on paper and/or via smartphone) and patient reported outcomes (using a web-based customized survey with patient access)
•  Define subpopulations with greater adjuvant benefit using acetylsalicylic acid

• Patients 45 years and older with histologically confirmed adenocarcinoma of the colon
• Patients with histologically confirmed adenocarcinoma of the colon
• Patients must have TNM stage that is one of the following: pT3-4; N0-2 and M0, or pT1-2 and N1-2 (UICC stage II and III) (in case of >1 tumour: more advanced tumour is stage II or III)
• Patients who have undergone curative radical resection (R0 resection) within 12 weeks prior to study entry
• Written informed consent according to national and local regulation

• Patients with rectal cancer (defined as tumour within 15 cm from the anal verge)
• Patients currently taking (low-dose) acetylsalicylic acid for any reason
• Patients currently taking oral anti-coagulants or use of LMWH
• Patients with a history of bleeding disorders or active gastric or duodenal ulcers
• Patients currently taking high dose systemic glucocorticoids. (≥ 30 mg predniso(lo)n or equivalent)
• Patients with (suspected) (non-) polyposis syndrome (FAP/AFAP, MAP, Lynch syndrome)
• Patients with >100 polyps of the colon or a known hereditary syndrome of the colon in a first degree family member (father/mother/brother/sister/son/daughter)
• Allergy or intolerance to salicylates
• Patients with local or distant recurrent disease
• Previous malignancies other than CIN, BCC or SCC with a disease free survival less than 5 years
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Patients will be randomised to either receive orally acetylsalicylic acid 80 mg once daily or placebo.

–Enrolment: 2018- 2021

–End of study 2026 (5 years follow-up)

Prof. Dr. Marc Peeters

Leids Universitair Medisch Centrum (LUMC), the Netherlands

UZA
AZ Klina,
AZ Monica
AZ Nikolaas
AZ Heilige Familie
SJK Bornem
AZ Maria Middelares
AZ Glorieux, AZ Sint-Lucas
AZ Sint-Blasius Dendermonde
AZ Sint Dimpna Geel
GZA Antwerpen
OLV van Lourdes zh Waregem
AZ Groeninge
AZ Alma Eeklo
RZ Sint-Trudo
Jessa Ziekenhuis
ZNA
RZ Heilig Hart Leuven
CHR Verviers
CHRIEC
CH de Mouscron
Clinique Saint-Pierre Ottignies
CHU Ambroise Paré
Clinique Saint-Luc Bouge
CH de l'Ardenne
Grand Hôpital de Charleroi