Study on Aspirin Versus Placebo in Resected Colon Cancer With PI3K Mutation Stage III or II High Risk

Study Overview
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Brief Summary
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Four retrospective studies were recently published on efficacy of aspirin in patients with surgically resected colon cancer. Two of these studies strongly suggested that aspirin used in low doses (100 mg/d) after surgical resection of colorectal cancer with PI3K mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. The other two studies did not confirm the benefit of aspirin in this situation. These four retrospective studies provide an insufficient level of evidence to demonstrate the benefit of low-dose aspirin as adjuvant to surgery for colorectal cancer. Therefore, it is necessary as recommended in the conclusion of these studies and meta-analyses to perform a randomised prospective study to validate these data.

Official Title
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French Prospective Randomised Double Blind Study, on Aspirin Versus Placebo in Resected Colon Cancer With PI3K Mutation

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: aspirin intake
* Drug: placebo intake
* Procedure: Surgical resection of colonic adenocarcinoma stage III or II high risk
* Biological: Molecular analysis of exon 9 and 20 of PI3K
* Biological: blood intake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Colonic adenocarcinoma stage III Colonic adenocarcinoma stage II high risk MSS: T4bN0 or T4aN0 tumour penetrating the surface of the visceral peritoneum or less than 12 nodes evaluated; or with at least two of the following criteria:lymphatic involvement, perineural invasion, venous invasion or diagnosis of bowel obstruction or perforation; or poor differentiated tumour. PI3K mutation, exon 9 or 20 (tumour) Resection R0 WHO performance status 0-2 Chest and abdominal CT scan ≤ 8 weeks Life expectancy ≥ 3 years Written consent signed Exclusion Criteria: Anticoagulant and/or Antiaggregating treatment including clopidogrel Regular aspirin use (> 3 doses per week during more than 3 months the last year) Contraindication to Aspirin : Allergy to aspirin, Active or antecedent peptic ulcer Severe renal or hepatic insufficiency Pregnancy or nursing ongoing Rectal cancer Hereditary forms (i.e. lynch syndrome patients) Follow-up of the patient not feasible

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: Patient with aspirin intake<br>Surgical resection of colonic adenocarcinoma stage III or II high risk will be done in accordance with local guidelines. Molecular analysis of exon 9 and 20 of PI3K will be done using operative piece. If the mutation is detected, patient with colonic adenocarcinoma stage III or II high risk will take aspirin 100 mg/day during 3 years. Blood intake will be done every 6 months to evaluate patient compliance to treatment | Drug: aspirin intake<br>* Patient with colonic adenocarcinoma stage III or II high risk will take aspirin 100 mg/day during 3 years<br>Procedure: Surgical resection of colonic adenocarcinoma stage III or II high risk<br>* Surgical resection of colonic adenocarcinoma stage III or II high risk will be done in accordance with local guidelines<br>Biological: Molecular analysis of exon 9 and 20 of PI3K<br>* Molecular analysis of exon 9 and 20 of PI3K will be done using operative piece<br>Biological: blood intake<br>* Blood intake will be done every 6 months to evaluate patient compliance to treatment<br>|
| Placebo Comparator: Patient with placebo intake<br>Surgical resection of colonic adenocarcinoma stage III or II high risk will be done in accordance with local guidelines. Molecular analysis of exon 9 and 20 of PI3K will be done using operative piece. If the mutation is detected, patient with colonic adenocarcinoma stage III or II high risk will take placebo of aspirin 100 mg/day during 3 years. Blood intake will be done every 6 months to evaluate patient compliance to treatment | Drug: placebo intake<br>* Patient with colonic adenocarcinoma stage III or II high risk will take placebo of aspirin 100 mg/day during 3 years<br>Procedure: Surgical resection of colonic adenocarcinoma stage III or II high risk<br>* Surgical resection of colonic adenocarcinoma stage III or II high risk will be done in accordance with local guidelines<br>Biological: Molecular analysis of exon 9 and 20 of PI3K<br>* Molecular analysis of exon 9 and 20 of PI3K will be done using operative piece<br>Biological: blood intake<br>* Blood intake will be done every 6 months to evaluate patient compliance to treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient with local or distant recurrence or second colorectal cancer or death from any cause, whichever occurred first |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient with local or distant recurrence or second colorectal cancer or death from any cause, whichever occurred first |  | 5 years | 
| Number of alive patient |  | 5 years | 
| Number of pills taken by the patient for compliance evaluation | Number of pills taken by the patient will be assess in order to evaluate patient's compliance | every 6 months during 3 years | 
| Number of severe bleeding grade 3-4 events |  | 3 years | 
| Number of participants with treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pi3k mutation, Aspirin