Aspirin in Colorectal Cancer Liver Metastases

Phase 2

Active, not recruiting

• Conditions: Colorectal Cancer Liver Metastases; Colorectal Cancer; Liver Metastases
• Interventions: Drug: Acetylsalicylic acid; Drug: Placebo Oral Tablet

• Registration Number: NCT03326791
• Lead Sponsor: Oslo University Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-02
• Study First Submitted QC: 2017-10-25
• Study First Posted: 2017-10-31
• Study Start: 2017-12-15
• Primary Completion: 2022-02-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2023-12-13
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 466

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Acetylsalicylic acid	Acetylsalicylic acid 160 mg once daily until recurrent disease or a total period of 3 years.
Control group	Placebo Oral Tablet	Placebo Oral Tablet once daily until recurrent disease or a total period of 3 years.

Primary Outcome Measures

Name	Time	Method
Disease Free Survival (DFS) after three years treatment	3 years	DFS three years after initiation of treatment with ASA or Placebo after resection of liver metastases.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS) three years after treatment start	3 years	OS at three years after initiation of treatment with ASA or Placebo
Time to recurrence (TTR) of disease after randomization	3 years	Time to recurrence of liver metastases three years after start of treatment.
Health-related Quality of Life with 36-item Short Form Health Survey (SF-36)	3 years	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.
ASA in CRC and Cost-Effectiveness Analyses I	3 years	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.
ASA in CRC and Cost-Effectiveness Analyses III	3 years	Cost-effectiveness measured from a societal perspective by assessing records in Statistics Norway (SSB).
Health-related Quality of Life with EuroQoL 5 Dimensions (EQ-5D)	3 years	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).
ASA in CRC and Cost-Effectiveness Analyses II	3 years	Cost-effectiveness measured from a health care perspective by assessing the use of Health care provider in primary and specialized medicine.

Trial Locations

Locations (14)

Oslo University Hospital; 🇳🇴 Oslo, Norway

University Hospital of North-Norway; 🇳🇴 Tromsø, Norway

St Olavs Hospital; 🇳🇴 Trondheim, Norway

Linköping University Hospital; 🇸🇪 Linköping, Sweden

Skåne University Hospital Lund; 🇸🇪 Lund, Sweden

Sahlgranska University Hospital; 🇸🇪 Gothenburg, Sweden

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

University Hospital of Umeå; 🇸🇪 Umeå, Sweden

Rigshospitalet, Copenhagen; 🇩🇰 Copenhagen, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Haukeland University Hospital; 🇳🇴 Bergen, Norway

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Stavanger University Hospital; 🇳🇴 Stavanger, Norway