E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Colon or rectal cancer tumor stage II-III, tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN. |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 <60 should lead to consultation with a nephrologist. - Significant medical illness that would interfere with study participation - Pregnancy or breastfeeding females - Known allergy to NSAIDs or ASA - Current participation in another clinical trial that will be in conflict with the present study - Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study Patients with regular administration of ASA, defined as >3 doses/week, will be included in the observation group. Other additional regular use of ASA must be withdrawn before randomization. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time To Recurrence (TTR) at 3 years in patients with tumors harboring PIK3CA mutations in exon 9 and 20. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 years. Interim analyses on the safety endpoints after one year. |
|
E.5.2 | 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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 years. Interim analyses on the safety endpoints after one year. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Stratification based on clinical stage, cancer localisation (rectal/colon), type of mutation. |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 28 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |