Colon or rectal cancer tumor stage II-III, tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN.
Conditions
Interventions
Trade Name: Trombyl
Product Name: Trombyl
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Karolinska Institutet, Department of Molecular medicine and Surgery
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN - Colon cancer stage II-III or rectal cancer tumor stage I-III - Patient between18-80 years (including) - Radical surgery according to surgeon and pathologist - Karnofsky performance status =70% - Platelets = 100 x 109 / L - Clean Colonoscopy or Computed Tomography (CT) colon within 3 months preoperatively or postoperatively but before randomization - Patient able to swallow tablets - Patient able to understand and sign written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 360
Exclusion criteria
Exclusion criteria: - Hereditary colorectal cancer linked to familial colonic polyposis or Lynch syndrome - Inflammatory bowel disease (Crohn's disease or ulcerative colitis) - Distant metastases - Other cancers (excluding colorectal cancer or other skin cancer than melanoma) within 3 years from screening - Known bleeding diathesis (such as hemophilia) - Concomitant antiplatelet therapy (eg clopidrogrel or ticlopidine) or anticoagulant therapy (warfarin or low molecular weight heparin). Post-operative treatment with low molecular weight heparin must be withdrawn before administration of study treatment - Active gastritis or peptic ulcer, or significant surgical post-op bleeding, within the previous three months assessed at screening and randomization - Ongoing regular use of corticosteroids, Nonsteroidal Anti-Inflammatory Drug (NSAID) - Uncontrolled hypertension according to Investigator’s judgment - Clinically significant liver impairment according to Investigators judgment - Existing renal failure according to Investigator’s judgment. Renal failure with decreased creatinine clearance 3 doses/week, will be included in the observation group. Other additional regular use of ASA must be withdrawn before randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve Time To Recurrence (TTR) in patients with colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20) compared with placebo.;Secondary Objective: To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve Disease-Free Survival (DFS) in patients with colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20) compared with placebo. To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve DFS in patients with colorectal cancer with somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or PTEN genes compared with placebo. To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve TTR in patients with colorectal cancer with somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or PTEN genes compared with placebo To compare overall survival (OS) at 5 years from randomization in patients receiving low-dose ASA versus placebo. To assess overall safety and tolerability.;Primary end point(s): Time To Recurrence (TTR) at 3 years in patients with tumors harboring PIK3CA mutations in exon 9 and 20.;Timepoint(s) of evaluation of this end point: 3 years. Interim analyses on the safety endpoints after one year. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Disease-Free Survival (DFS) at 3 years, in patients with tumors harboring PIK3CA mutations in exon 9 and 20. Disease-Free Survival (DFS) at 3 years, in patients with tumors harboring PIK3CA mutations other than in exon 9 and 20 and in PIK3R1 and PTEN. Time To Recurrence (TTR) at 3 years, in patients with tumors harboring PIK3CA mutations other than in exon 9 and 20 and in PIK3R1 and PTEN. OS at 5 years in patients with tumors harboring PIK3CA mutations in exon 9 and 20, other than in exon 9 and 20, and in PIK3R1 and PTEN.;Timepoint(s) of evaluation of this end point: 3 years. Interim analyses on the safety endpoints after one year. | — |
Countries
Denmark, Finland, Norway, Sweden
Contacts
Public ContactCoordinating Investigator
Karolinska Institutet
Outcome results
None listed