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

Phase 3

• Conditions: Colorectal Cancer
• Interventions: 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

• Registration Number: NCT02945033
• Lead Sponsor: University Hospital, Rouen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-20
• Study First Submitted QC: 2016-10-24
• Study First Posted: 2016-10-26
• Study Start: 2018-07-12
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-23
• Last Update Posted: 2019-10-24
• Primary Completion: 2024-07
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 264

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patient with aspirin intake	aspirin intake	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
Patient with aspirin intake	Surgical resection of colonic adenocarcinoma stage III or II high risk	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
Patient with aspirin intake	Molecular analysis of exon 9 and 20 of PI3K	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
Patient with placebo intake	Surgical resection of colonic adenocarcinoma stage III or II high risk	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
Patient with placebo intake	blood intake	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
Patient with aspirin intake	blood intake	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
Patient with placebo intake	placebo intake	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
Patient with placebo intake	Molecular analysis of exon 9 and 20 of PI3K	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 severe bleeding grade 3-4 events	3 years
Number of participants with treatment-related adverse events	3 years	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Number of pills taken by the patient for compliance evaluation	every 6 months during 3 years	Number of pills taken by the patient will be assess in order to evaluate patient's compliance

Trial Locations

Locations (1)

Rouen University Hospital; 🇫🇷 Rouen, France