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Aspirin in Colorectal Cancer Liver Metastases (ASAC)

Primary Purpose

Colorectal Cancer Liver Metastases, Colorectal Cancer, Liver Metastases

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Acetylsalicylic acid
Placebo Oral Tablet
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Cancer Liver Metastases focused on measuring Acetylsalicylic acid, Aspirin, Trombyl, Secondary prevention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Aarhus University Hospital
  • Rigshospitalet, Copenhagen
  • Odense University Hospital
  • Haukeland University Hospital
  • Oslo University Hospital
  • Stavanger University Hospital
  • University Hospital of North-Norway
  • St Olavs Hospital
  • Sahlgranska University Hospital
  • Linköping University Hospital
  • Skåne University Hospital Lund
  • Karolinska University Hospital
  • University Hospital of Umeå
  • Uppsala University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention group

Control group

Arm Description

Acetylsalicylic acid 160 mg once daily until recurrent disease or a total period of 3 years.

Placebo Oral Tablet once daily until recurrent disease or a total period of 3 years.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time to recurrence (TTR) of disease after randomization
Time to recurrence of liver metastases three years after start of treatment.
Overall survival (OS) three years after treatment start
OS at three years after initiation of treatment with ASA or Placebo
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.
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).
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.
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.
ASA in CRC and Cost-Effectiveness Analyses III
Cost-effectiveness measured from a societal perspective by assessing records in Statistics Norway (SSB).

Full Information

First Posted
October 2, 2017
Last Updated
October 19, 2022
Sponsor
Oslo University Hospital
Collaborators
Norwegian Cancer Society, The Research Council of Norway, Klinbeforsk
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1. Study Identification

Unique Protocol Identification Number
NCT03326791
Brief Title
Aspirin in Colorectal Cancer Liver Metastases
Acronym
ASAC
Official Title
Acetylsalicylic Acid as Secondary Prevention in Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 15, 2017 (Actual)
Primary Completion Date
February 1, 2022 (Actual)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
Norwegian Cancer Society, The Research Council of Norway, Klinbeforsk

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Liver Metastases, Colorectal Cancer, Liver Metastases
Keywords
Acetylsalicylic acid, Aspirin, Trombyl, Secondary prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Multi-centre, double-blinded, randomized, placebo-controlled clinical intervention trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Eligible patients will be allocated in a 1:1 ratio using a computer randomization procedure stratified by centre. The randomization will be blocked within each stratum.
Allocation
Randomized
Enrollment
466 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Acetylsalicylic acid 160 mg once daily until recurrent disease or a total period of 3 years.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Placebo Oral Tablet once daily until recurrent disease or a total period of 3 years.
Intervention Type
Drug
Intervention Name(s)
Acetylsalicylic acid
Other Intervention Name(s)
Trombyl, Aspirin
Intervention Description
Trombyl 160 mg once daily
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Placebo one tablet daily
Primary Outcome Measure Information:
Title
Disease Free Survival (DFS) after three years treatment
Description
DFS three years after initiation of treatment with ASA or Placebo after resection of liver metastases.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Time to recurrence (TTR) of disease after randomization
Description
Time to recurrence of liver metastases three years after start of treatment.
Time Frame
3 years
Title
Overall survival (OS) three years after treatment start
Description
OS at three years after initiation of treatment with ASA or Placebo
Time Frame
3 years
Title
Health-related Quality of Life with 36-item Short Form Health Survey (SF-36)
Description
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.
Time Frame
3 years
Title
Health-related Quality of Life with EuroQoL 5 Dimensions (EQ-5D)
Description
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).
Time Frame
3 years
Title
ASA in CRC and Cost-Effectiveness Analyses I
Description
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.
Time Frame
3 years
Title
ASA in CRC and Cost-Effectiveness Analyses II
Description
Cost-effectiveness measured from a health care perspective by assessing the use of Health care provider in primary and specialized medicine.
Time Frame
3 years
Title
ASA in CRC and Cost-Effectiveness Analyses III
Description
Cost-effectiveness measured from a societal perspective by assessing records in Statistics Norway (SSB).
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kjetil Taskèn, MD PhD
Organizational Affiliation
University of Oslo
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sheraz Yaqub, MD PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Facility Name
Rigshospitalet, Copenhagen
City
Copenhagen
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Stavanger University Hospital
City
Stavanger
Country
Norway
Facility Name
University Hospital of North-Norway
City
Tromsø
Country
Norway
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Facility Name
Sahlgranska University Hospital
City
Gothenburg
Country
Sweden
Facility Name
Linköping University Hospital
City
Linköping
Country
Sweden
Facility Name
Skåne University Hospital Lund
City
Lund
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Facility Name
University Hospital of Umeå
City
Umeå
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
34544470
Citation
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.
Results Reference
derived
Links:
URL
http://www.asac.no/
Description
Website
URL
https://kliniskestudier.helsenorge.no/tykktarmskreft-kan-acetylsalisylsyre-hindre-tilbakefall-av-spredning
Description
Related Info

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Aspirin in Colorectal Cancer Liver Metastases

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