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

University Hospital, Rouen

Status and phase: Enrolling; Phase 3

Conditions: Colorectal Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02945033

2015/222/HP

Details and patient eligibility

About

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.

Enrollment: 264 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

264 participants in 2 patient groups, including a placebo group

Patient with aspirin intake

Experimental group

Description:

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

Treatment:

Biological: blood intake

Biological: Molecular analysis of exon 9 and 20 of PI3K

Procedure: Surgical resection of colonic adenocarcinoma stage III or II high risk

Drug: aspirin intake

Patient with placebo intake

Placebo Comparator group

Description:

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

Treatment:

Biological: blood intake

Biological: Molecular analysis of exon 9 and 20 of PI3K

Drug: placebo intake

Procedure: Surgical resection of colonic adenocarcinoma stage III or II high risk