Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers

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

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)

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

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)