Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers

Study Overview
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Brief Summary
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We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control. If indeed found to be beneficial, because aspirin is cheap and easy to administer, it will positively impact the lives of many individuals in Asia and globally. STUDY OBJECTIVE To assess the effectiveness of Aspirin against placebo control in patients with dukes C or high risk dukes B colorectal cancer in terms of Disease Free Survival (DFS) and Overall Survival (OS) Primary endpoints DFS among all eligible subjects (high risk Dukes B colon cancer, Dukes C colon cancer and rectal cancer patient sub-groups); DFS among patients with colon cancer (high-risk Dukes B and Dukes C colon cancer). Secondary endpoints Overall survival (OS) over 5 years DFS and OS in Chinese, Malay, Indian and other ethnic groups Resected high risk Dukes B colon cancer, Dukes C colon cancer and rectal cancer sub-groups, individually Compliant versus non-compliant subjects PIK3CA mutated tumors (where samples are available)

Detailed Description
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Aspirin in patients with dukes C or high risk dukes B colorectal cancer can improve survival in this patient population over placebo control. Eligible patients will be randomized to treatment arms, using the following stratification factors: Study Centre Tumour Type Type of adjuvant chemotherapy received(exposed/not exposed to oxaliplatin Patients will be randomized over a 5 years' time period. After randomization, patient will have 3 monthly assessments with treatment for 3 years followed by 6 monthly assessments for additional 2 years follow-up

Official Title
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Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers - An International, Multi-Center, Double Blind, Randomized Placebo Controlled Phase III Trial

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Other: placebo
* Drug: Acetylsalicylic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female outpatient of ≥ 18 years of age or ≥ country's legal age for adult consent Dukes C colon cancer, high risk Dukes B colon cancer, Dukes B rectal cancer or Dukes C rectal cancer (see Appendix 1 for definition of High Risk Dukes B) Undergone complete resection of primary tumour Completed standard therapy ( at least 3 months of chemotherapy ± radiotherapy ) Within 120 days of completion of standard therapy (surgery, chemotherapy ± radiotherapy) ECOG performance status 0 to 2 Satisfactory haematological or biochemical functions (tests should be carried out within 8 weeks prior to randomisation): Results of clinical investigations carried out within 8 weeks prior to randomisation can be used in place of the required screening investigations. Patients with mild laboratory abnormalities can be included at the discretion by the site principal investigator, and after approval by ASCOLT Trial Management Group ANC ≥ 1.0 x 109/L Platelets ≥ 100 x 109/L Creatinine clearance ≥ 30 mL/min Total bilirubin ≤ 2.0 x the upper limit normal AST & ALT ≤ 5 x the upper limit normal Completed the following investigations Colonoscopy(or CT colonogram(within 16 months prior to randomization) Imaging of abdomen (CT or CT colonogram or MRI or PET or Ultrasound) within 16 months prior to randomization Written informed consent Exclusion Criteria Pre-existing Familial adenomatous polyposis, inflammatory bowel disease or ulcerative colitis Active gastritis or active peptic ulcer History of continuous daily use of PPI more than 1 year prior to consent Gastrointestinal bleeding within the past one year Haemorrhagic diathesis (i.e. haemophilia) Uncontrolled hypertension (untreated systolic blood pressure > 160 mmHg, or diastolic blood pressure > 95 mmHg) History of recent cancers (except for colorectal cancers, non-melanoma skin cancers, basal cell carcinomas, squamous cell carcinomas) in the past 5 years History of stroke, coronary arterial disease, angina, or vascular disease Patients who are on current long term treatment (≥ 4 consecutive weeks) with Aspirin, NSAID or Cox-2 inhibitors History of erosive GERD or active erosive GERD on gastroscopy. Patient on active current treatment of antiplatelet agents (i.e. off-study Aspirin, clopidogrel, ticlopidine) Patient receiving active treatment of anticoagulants (i.e. warfarin, low molecular weight heparins) Pregnant, lactating, or not using adequate contraception Patient having known allergy to NSAID or Aspirin Unexplained rise of CEA (i.e. smoker with elevated CEA will not be excluded) Patient on other investigational drug Patients with HNPCC (Lynch Syndrome)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acetylsalicylic acid<br>200mg OD for 3 years | Drug: Acetylsalicylic acid<br>* Adjuvant Therapy<br>* Other names: Aspirin;|
| Placebo Comparator: Placebo<br>200mg OD for 3 years | Other: placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II colon cancer, stage III colon cancer, stage II rectal cancer, stage III rectal cancer