Aspirin in Colorectal Cancer Liver Metastases (ASAC)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer Liver Metastases; Colorectal Cancer; Liver Metastases	Drug: Acetylsalicylic acid; Drug: Placebo Oral Tablet	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	800 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Multi-centre, double-blinded, randomized, placebo-controlled clinical intervention trial.
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
Primary Purpose:	Prevention
Official Title:	Acetylsalicylic Acid as Secondary Prevention in Colorectal Cancer
Actual Study Start Date :	December 15, 2017
Estimated Primary Completion Date :	October 2023
Estimated Study Completion Date :	October 2023

Arms and Interventions

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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: Trombyl; Aspirin
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

Outcome Measures

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Primary Outcome Measures :

1. Disease Free Survival (DFS) after three years treatment [ Time Frame: 3 years ]
   DFS three years after initiation of treatment with ASA or Placebo after resection of liver metastases.

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• First time CRCLM (synchronous or metachronous).
• Recurrence of CRCLM (not previously included in this trial).
• 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.
• 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.

Contacts and Locations

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Contacts

Contact: Anja Kokvoll, Nurse	+4747908528	anjkok@ous-hf.no
Contact: Victoria Bringsjord, Nurse	+4747908528	vicbri@ous-hf.no

Locations

Denmark
Aarhus University Hospital	Not yet recruiting
Aarhus, Denmark
Contact: Frank V Mortensen, MD PhD +4578459006 franmort@rm.dk
Rigshospitalet, Copenhagen	Not yet recruiting
Copenhagen, Denmark
Contact: Peter N Larsen, MD PhD +4527104290
Odense University Hospital	Not yet recruiting
Odense, Denmark
Contact: Claus Fristrup, MD PhD Claus.Wilki.Fristrup@rsyd.dk
Norway
Haukeland University Hospital	Not yet recruiting
Bergen, Norway
Contact: Arild Horn, MD PhD +4792034290 arild.horn@helse-bergen.no
Oslo University Hospital	Recruiting
Oslo, Norway
Contact: Sheraz Yaqub, MD PhD +4790953996 shya@ous-hf.no
Contact: Bjørn A Bjørnbeth, MD PhD +4747287853 bbjoer@ous-hf.no
Stavanger University Hospital	Not yet recruiting
Stavanger, Norway
Contact: Jon Arne Søreide, MD PhD +4790531770 jonarne.soreide@mac.com
University Hospital of North-Norway	Not yet recruiting
Tromsø, Norway
Contact: Kim Erlend Mortensen, MD PhD Kim.Erlend.Mortensen@unn.no
St Olavs Hospital	Not yet recruiting
Trondheim, Norway
Contact: Jon Erik Grønbech, MD PhD +4790546058 jon.e.gronbech@ntnu.no
Sweden
Sahlgranska University Hospital	Not yet recruiting
Gothenburg, Sweden
Contact: Magnus Rizell, MD PhD +46705259301 magnus.rizell@surgery.gu.se
Linköping University Hospital	Recruiting
Linköping, Sweden
Contact: Per Sandström, MD PhD per.sandstrom@liu.se
Skåne University Hospital Lund	Not yet recruiting
Lund, Sweden
Contact: Gert Lindell, MD PhD +4646176288 gert.lindell@med.lu.se
Karolinska University Hospital	Recruiting
Stockholm, Sweden
Contact: Ernesto Sparelid, MD PhD ernesto.sparrelid@ki.se
University Hospital of Umeå	Not yet recruiting
Umeå, Sweden
Contact: Oskar Hemmingsson, MD PhD oskar.hemmingsson@umu.se
Uppsala University Hospital	Not yet recruiting
Uppsala, Sweden
Contact: Bengt Isaksson, MD PhD +46736994477

Sponsors and Collaborators

Oslo University Hospital

Norwegian Cancer Society

The Research Council of Norway

KLINBEFORSK

Investigators

Principal Investigator:	Bjørn A Bjørnbeth, MD PhD	Oslo University Hospital
Principal Investigator:	Kjetil Taskèn, MD PhD	University of Oslo
Principal Investigator:	Sheraz Yaqub, MD PhD	Oslo University Hospital

More Information

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Additional Information:

Website 

Related Info 

Responsible Party:	Sheraz Yaqub, MD PhD, Coordinating Investigator, Oslo University Hospital
ClinicalTrials.gov Identifier:	NCT03326791 History of Changes
Other Study ID Numbers:	2014/2217
First Posted:	October 31, 2017
Last Update Posted:	January 23, 2018
Last Verified:	January 2018

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

Keywords provided by Sheraz Yaqub, Oslo University Hospital:

Acetylsalicylic acid; Aspirin; Trombyl; Secondary prevention

Additional relevant MeSH terms:

Aspirin; Colorectal Neoplasms; Colonic Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Liver Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases	Rectal Diseases; Neoplastic Processes; Pathologic Processes; Liver Diseases; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action