Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial

Sheraz Yaqub,Oddvar Sandvik ,Ernesto Sparrelid,Oskar Hemmingsson,Helena Taflin,Jon Erik Grønbech ,Per Sandström,Frank Viborg Mortensen,Ingebjørg S Juel ,Kjetil Taskén,Bengt Isaksson,Bjørn Atle Bjørnbeth,Gert Lindell,Jon-Helge Angelsen,Kim Erlend Mortensen,Claus Wilki Fristrup,Magnus Rizell,Peter Nørgaard Larsen

doi:10.1186/s13063-021-05587-w

Abstract

BackgroundColorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver.MethodsThe ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines.DiscussionThe ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness.Trial registrationClinicalTrials.gov NCT03326791. Registered on 31 October 2017.

Highlights

Background and rationale {6a} Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic disease is the most common cause of death in these patients [1]
A number of reports have shown that intake of non-steroidal antiinflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) inhibiting cyclooxygenases (COX) reduce the risk of CRC development [5,6,7]
Recent metaanalyses of 5 to 51 different interventional studies with ASA originally conducted for cardiovascular indications and with 5 to 20 years follow-up have indicated, when they were re-analysed and linked with cancer registry data, that ASA reduced the risk of later CRC with hazard ratios of 0.45 to 0.75 for cumulative incidence and mortality and with doses as low as 75 mg per day, and with increasing benefit with duration of treatment [9,10,11]

Summary

Methods

The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines

Discussion

Introduction

Statistical methods

Findings