Aspirin in Colorectal Cancer Liver Metastases (ASAC)

Acetylsalicylic Acid as Secondary Prevention in Colorectal Cancer

The ASAC trial is a Scandinavian, multi-center, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose acetylsalicylic acid (ASA) can improve disease free survival in patients treated with resection for colorectal cancer liver metastases (CRCLM).

Several studies have shown beneficial effect of ASA on primary prevention of CRC and the investigators group and others have shown a potential association of ASA also taken after the diagnosis on CRC survival in registry-based studies (secondary prevention). 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 till disease recurrence. The patients will be treated and followed up according to standard of care and the National Guidelines.

The ASAC trial will be the first clinical interventional trial to assess the beneficial role of ASA in recurrence of CRC liver metastases and survival. ASA is an inexpensive, well tolerated, and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRC liver metastases if the study shows a beneficial effect. This trial will also investigate the effect of ASA as adjuvant treatment on Health-related Quality of Life and the cost-effectiveness.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Liver Metastases; Colorectal Cancer Liver Metastases
• Intervention / Treatment: Drug: Acetylsalicylic acid; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 466
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet, Copenhagen
  • Odense, Denmark
    • Odense University Hospital
• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Oslo, Norway
    • Oslo University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
  • Tromsø, Norway
    • University Hospital of North-Norway
  • Trondheim, Norway
    • St Olavs hospital
• Sweden
  • Gothenburg, Sweden
    • Sahlgranska University Hospital
  • Linköping, Sweden
    • Linköping University Hospital
  • Lund, Sweden
    • Skane University Hospital Lund
  • Stockholm, Sweden
    • Karolinska University Hospital
  • Umeå, Sweden
    • University Hospital of Umeå
  • Uppsala, Sweden
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• First time CRCLM (synchronous or metachronous).
• Recurrence of CRCLM (not previously included in this trial).
• In synchronous CRCLM and "Liver first" approach, the primary tumor must be resected within 6 weeks after the liver
• Macroscopic (surgical) free resection margins (R0 or R1 resection).
• Must be ambulatory with a performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
• Must be at least 18 years of age.
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization - Good Clinical Practice (ICH GCP), and national/local regulations.

Exclusion Criteria:

• Concomitant use of ASA or other anticoagulants or platelet inhibitors such as warfarin or clopidogrel.
• Ongoing regular use of corticosteroids or NSAIDs.
• Inherited or acquired coagulopathy (haemophilia).
• Blood platelets (thrombocytes) < 100 x 10^9/L.
• Severe heart failure (classified as New York Heart Association (NYHA) class >III)
• Severe kidney failure >Stage 3b
• CRCLM previously treated with radiofrequency or microwave ablation technique
• Pregnancy or breastfeeding. For women in childbearing age there will be pregnancy test at monthly intervals (urine human chorionic gonadotropin (HCG) pregnancy tests (for home testing) will be given to the patients for monthly tests and the patient will self-report the results at each control). Furthermore, highly effective contraceptives will be required.
• Childbearing potential without proper contraceptive measures such as oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device to avoid pregnancy for the entire study period.
• Liver cirrhosis with a Child-Pugh score >B7.
• Alcoholism.
• Contraindication listed on the Summary of Product Characteristics (SmPC) of Trombyl: Hypersensitivity/allergies to ASA, Thrombocytopenia, Previous severe gastrointestinal haemorrhage/peptic ulcer due to ASA/NSAID, Active peptic ulcer, Haemophilia, Liver cirrhosis, Severe congestive heart failure.
• Need to use concomitant medications contraindicated according to SmPC of Trombyl.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Acetylsalicylic acid 160 mg once daily until recurrent disease or a total period of 3 years.	Drug: Acetylsalicylic acid; Trombyl 160 mg once daily; Other Names: Aspirin; Trombyl
Placebo Comparator: Control group; Placebo Oral Tablet once daily until recurrent disease or a total period of 3 years.	Drug: Placebo Oral Tablet; Placebo one tablet daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS) after three years treatment	DFS three years after initiation of treatment with ASA or Placebo after resection of liver metastases.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recurrence (TTR) of disease after randomization	Time to recurrence of liver metastases three years after start of treatment.	3 years
Overall survival (OS) three years after treatment start	OS at three years after initiation of treatment with ASA or Placebo	3 years
Health-related Quality of Life with 36-item Short Form Health Survey (SF-36)	SF-36 has been proven useful in monitoring population health, estimating the burdens of different diseases, monitoring outcome in clinical practice, and evaluating medical treatment effects. Health-related Quality of Life (HR-QoL) will be assessed with SF-36.	3 years
Health-related Quality of Life with EuroQoL 5 Dimensions (EQ-5D)	The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. This will be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions will be presented as a health profile. Health-related Quality of Life (HR-QoL) will be assessed with EuroQoL 5 Dimensions (EQ-5D).	3 years
ASA in CRC and Cost-Effectiveness Analyses I	Changes in HR-QoL will be used in calculation of the quality-adjusted life-year (QALY), a key outcome used in economic evaluations to compare treatments.	3 years
ASA in CRC and Cost-Effectiveness Analyses II	Cost-effectiveness measured from a health care perspective by assessing the use of Health care provider in primary and specialized medicine.	3 years
ASA in CRC and Cost-Effectiveness Analyses III	Cost-effectiveness measured from a societal perspective by assessing records in Statistics Norway (SSB).	3 years

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: The Research Council of Norway; Norwegian Cancer Society; Klinbeforsk
• Investigators: Principal Investigator: Kjetil Taskèn, MD PhD, University of Oslo; Principal Investigator: Sheraz Yaqub, MD PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Yaqub S, Bjornbeth BA, Angelsen JH, Fristrup CW, Gronbech JE, Hemmingsson O, Isaksson B, Juel IS, Larsen PN, Lindell G, Mortensen FV, Mortensen KE, Rizell M, Sandstrom P, Sandvik OM, Sparrelid E, Taflin H, Tasken K; ASAC study group. Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial. Trials. 2021 Sep 20;22(1):642. doi: 10.1186/s13063-021-05587-w.

Helpful Links

• Website
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): February 1, 2022
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Aspirin; Secondary prevention; Acetylsalicylic acid; Trombyl
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Liver Diseases; Colonic Diseases; Neoplastic Processes; Neoplasms, Second Primary; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Aspirin
• Other Study ID Numbers: 2014/2217

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No