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

Abstract Background: Colorectal 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 treatment of choice although almost half of the resected patients get recurrence in the liver.Methods: The ASAC trial is a Scandinavian, multi-centre, 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: The 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 registration: ClinicalTrials.gov Identifier: NCT03326791. Registered 31 October 2017, https://clinicaltrials.gov/ct2/show/NCT03326791?term=asac&draw=2&rank=1

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

Trials ◽

10.1186/s13063-021-05587-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sheraz Yaqub ◽

Bjørn Atle Bjørnbeth ◽

Jon-Helge Angelsen ◽

Claus Wilki Fristrup ◽

Jon Erik Grønbech ◽

...

Keyword(s):

Colorectal Cancer ◽

Secondary Prevention ◽

Liver Metastases ◽

Adjuvant Treatment ◽

Controlled Trial ◽

Disease Free Survival ◽

Controlled Study ◽

Western World ◽

National Guidelines ◽

Colorectal Cancer Liver Metastases

Abstract Background Colorectal 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. 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 The 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 registration ClinicalTrials.gov NCT03326791. Registered on 31 October 2017.

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Aspirin as adjuvant treatment for colorectal cancer: Rationale and progress of the Add-Aspirin trial.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps3624 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS3624-TPS3624

Author(s):

Ruth E Langley ◽

Richard H. Wilson ◽

Fay Helen Cafferty ◽

Nalinie Joharatnam ◽

Janet Shirley Graham ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Treatment ◽

Controlled Trial ◽

Disease Free Survival ◽

Mechanisms Of Action ◽

Subsequent Treatment ◽

Phase Iii ◽

Double Blind ◽

Pik3ca Mutations ◽

The Impact

TPS3624 Background: There is now a body of evidence indicating a potential role for aspirin in colorectal cancer (CRC) prevention. In cardiovascular trials, effects on incidence of cancer metastases and short-term mortality suggest further possible roles in the treatment setting, supported by observational studies of aspirin use after cancer diagnosis. In the prevention setting, aspirin use has been limited by toxicity concerns, particularly of serious bleeding. In the adjuvant setting, benefits associated with reducing recurrence and subsequent treatment may outweigh these risks. The Add-Aspirin trial will investigate this, and will also consider possible mechanisms of action for aspirin effects, including the impact of PIK3CA mutations, where there are currently several theories and conflicting data. Methods: Add-Aspirin (ISRCTN74358648) is an international, phase III, double-blind, randomised, placebo-controlled trial recruiting patients who have undergone surgery and relevant adjuvant treatment for stage II or III CRC, as well as those with completely resected CRC liver metastases. Parallel randomised cohorts will address the question in breast, gastro-oesophageal and prostate cancer. Participants take aspirin 100mg daily for an 8-week run-in, to assess adherence and toxicity, and those suitable to proceed are randomised (1:1:1) to aspirin 100mg, aspirin 300mg or placebo daily for at least 5 years. A number of measures – including blood pressure control and PPI use where relevant - are in place to reduce bleeding risk. The primary outcome is disease-free survival (target hazard ratio = 0.8, n = 2600 in 5 years) with a long term analysis of survival planned across the tumour groups. Translational work includes a sub-study monitoring urinary thromboxane B2 as a marker of platelet activation in a subgroup (n = 500) to investigate mechanisms of action. Add-Aspirin opened in 2015 and recruited 1505 CRC patients during the first 3 years from 137 UK centres. 1282 (85%) proceeded to randomisation. A pre-planned feasibility analysis of run-in data (n = 2253 across all 4 tumour groups) provided reassuring data on safety, tolerability and adherence, and recruitment continues with centres in India and Republic of Ireland recently joining. Clinical trial information: 74358648.

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