Clinical trial NCT03326791: Aspirin in Colorectal Cancer Liver Metastases
Official title: Acetylsalicylic Acid as Secondary Prevention in Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer Liver Metastases
Colorectal Cancer
Liver Metastases
Keywords: Acetylsalicylic acid
Aspirin
Trombyl
Secondary prevention
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Norwegian Cancer Society
name: The Research Council of Norway
name: Klinbeforsk
First posted: 2017-10-31
Enrollment: 466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-centre, double-blinded, randomized, placebo-controlled clinical intervention trial.
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Disease Free Survival (DFS) after three years treatment
timeFrame: 3 years
Secondary outcomes:
measure: Time to recurrence (TTR) of disease after randomization
timeFrame: 3 years
measure: Overall survival (OS) three years after treatment start
timeFrame: 3 years
measure: Health-related Quality of Life with 36-item Short Form Health Survey (SF-36)
timeFrame: 3 years
measure: Health-related Quality of Life with EuroQoL 5 Dimensions (EQ-5D)
timeFrame: 3 years
measure: ASA in CRC and Cost-Effectiveness Analyses I
timeFrame: 3 years
measure: ASA in CRC and Cost-Effectiveness Analyses II
timeFrame: 3 years
measure: ASA in CRC and Cost-Effectiveness Analyses III
timeFrame: 3 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Copenhagen
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North-Norway
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Gothenburg
country: Sweden
facility: Sahlgranska University Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital Lund
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: University Hospital of Umeå
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: University of Oslo
name: Kjetil Taskèn, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Sheraz Yaqub, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.