Aspirin for recurrence and survival in colon cancer
A Phase III Double-blind Placebo-controlled Randomised Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients (ASPIRIN).
- Digestive cancer
Why this trial?
Colorectal cancer is one of the most common cancers in developed countries, with about 1 million new cases each year and a mortality rate of nearly 33%. In Europe, colorectal cancer is the second most common cause of death by cancer, with a 5-year overall survival rate of approximately 66-67%. The incidence of is expected to increase.
Initial therapy after diagnosis usually comprises primary surgical resection, followed by adjuvant chemotherapy for patients that have stage II, III and IV cancer in order to prevent metastasis. However, despite encouraging advances in surgical techniques and improved therapeutic protocols, more than half of patients with colorectal cancer eventually develop metastasis, leading to death in 20 - 35% of stage II and III patients.
There is a clear need for better treatment options that prevent the recurrence of colon cancer after initial surgery.
Why this drug?
The rationale for conducting this trial with aspirin is based mainly on 3 publications. Sandler et al. (2003) conducted a randomised trial showing that daily use of aspirin was associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer. A pooled analysis by Rothwell et al. (2010) of 5 randomised trials investigating the cardiovascular effects of aspirin with a 20-year follow-up period, showed that aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality of colorectal cancer. Furthermore, Rothwell et al. (2012) retrospectively analysed the data of 5 large randomised trials of daily aspirin administration (≥75 mg daily) versus control for the prevention of cardiovascular events in the UK. Based on their findings, they concluded that aspirin may prevent distant metastasis in colorectal cancer patients.
As a result, many epidemiological and molecular retrospective studies have been published in the past several years. It is important to verify these data by means of randomised clinical trials to prove the role of aspirin in the adjuvant treatment of cancer. If acetylsalicylic acid is proven beneficial, it has the potential to change treatment paradigms, with significant global health and socio-economic impact. Acetylsalicylic acid is off-patent and inexpensive - in an era of escalating cancer treatment costs, providing the evidence for cost-competitive solutions is imperative. Scientific proof of a notable therapeutic effect of a well-tolerated, cheap drug like aspirin will be a major step forward in the battle against colon cancer.
This is a phase III double-blind, placebo-controlled, randomised trial of adjuvant low-dose acetylsalicylic acid in patients with stage II and III colon cancer. The primary objective is to study the effect of 80mg acetylsalicylic acid (given orally once daily for 5 years) on 5-year overall survival. 1588 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. Study medication will be continued for 5 years. In the Netherlands, 1188 patients will be recruited by 35 centres and the remaining 400 patients will be recruited by 10 Belgian centres.
ASPIRIN trial in Belgium:
- Coordinating Investigator: Prof. Dr. M. Peeters, Oncology Dept., University Hospital Antwerp, UZA, Edegem, Belgium
- Sponsor: University Hospital Antwerp, UZA, Edegem, Belgium
- Other funding partner: Kom Op Tegen Kanker
ASPIRIN trial in the Netherlands:
- Principal Investigators: Dr. G.J. Liefers, Dept. Surgical Oncology, LUMC, Leiden; Dr. J.E.A. Portielje, Dept. Medical Oncology, HAGA; Prof. Dr. R. Fodde, Dept. Pathology, Erasmus MC, The Netherlands
- Sponsor: Leiden University Medical Center, Leiden, The Netherlands
More info on clinicaltrials.gov: NCT03464305 (Belgium)
Cole, B. F., et al. (2009). Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. Journal of the National Cancer Institute, 101(4), 256-66. doi: 10.1093/jnci/djn485
Cunningham, D., et al. (2010). Colorectal cancer. Lancet, 375(9719): 1030-1047. doi: 10.1016/S0140-6736(10)60353-4
Rothwell, P. M., et al. (2012). Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 379(9826):1602-12. doi: 10.1016/S0140-6736(11)61720-0
Rothwell, P. M., et al. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet, 379(9826): 1591-1601. doi: 10.1016/S0140-6736(12)60209-8
Rothwell, P. M., et al. (2010). Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet, 376(9754): 1741-1750. doi: 10.1016/S0140-6736(10)61543-7
Author: Kristine Beckers (Trial Manager)
Last updated: June 2018.