E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk stage III colon cancer in adjuvant setting |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009955 |
E.1.2 | Term | Colon cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 compare the 3-year Disease Free Survival rate. |
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E.2.2 | Secondary objectives of the trial |
• Evaluation of Efficacy: Disease-free-Survival at 2 years. • Overall Survival (OS) • Evaluation of Toxicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient ≥18 years and < 71years 2. Patient with ECOG ≤1 3. Pathologically confirmed high-risk stage III colon adenocarcinoma, restricted to pT4N1 or pT1-4N2 tumor. 4. Curative R0 surgical resection within 42 days before randomization. 5. Patients who have undergone surgery for colon cancer, defined as a tumor location >12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery (high rectum), without gross or microscopic evidence of residual disease after surgery with curative intent 6. Start of study drug treatment has to be performed less than 56 days after surgery. 7. No prior chemotherapy. 8. No prior abdominal or pelvic irradiation. 9. Patient with adequate organ function: Absolute neutrophil count (ANC) ≥1.5 x 109/L Haemoglobin ≥9 g/dL Platelets (PTL) ≥100 x 109/L AST/ALT ≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN Total Bilirubin ≤1.5 x ULN (Upper Limit of Normal) Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula) Carcinoembryogenic antigen (CEA) ≤10ng/mL after surgery (during screening period) 10. Adequate contraception if applicable. 11. Patient able and willing to comply with study procedures as per protocol 12. Patient able to understand and willing to sign and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures 13. Public or private health insurance coverage 14. Life expectancy of > or = at 5 years
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E.4 | Principal exclusion criteria |
1. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study 2. Metastatic disease 3. Presence of inflammatory bowel disease 4. Known hypersensitivity reaction to any of the components of study treatments. 5. Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period 6. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia 7. Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix 8. Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent 9. History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v4.03. 10. Any significant disease which, in the investigator’s opinion, would exclude the patient from the study. 11. Known DPD deficiency or UGTA1A1 homozygous 7/7 12. Patients already included in another therapeutic trial involving an experimental drug
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is the Disease Free Survival (DFS) at 3 years, defined as the time from the date of randomization up to the date of: - first local, regional or distant relapse; - second colorectal cancer; - death from any cause included treatment-related death. Other primary cancer (except second primary colorectal) will be ignored. Second primary cancer will be recorded to have the opportunity of evaluating other definition of DFS.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 years from the date of randomization |
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E.5.2 | Secondary end point(s) |
Evaluation of Efficacy: The evaluation of efficacy is defined as the Disease Free Survival at 2 years, defined as the time from the date of randomization up to the date of: - first local, regional or distant relapse - second colorectal cancer - death from any cause included treatment-related death. Other primary cancer (except second primary colorectal) will be ignored. Second primary cancer will be recorded to have the opportunity of evaluating other definition of DFS
Overall Survival (OS): Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause.
Evaluation of Toxicity: Safety of the study treatment will be assessed on occurrence of Adverse Events (AEs), intake of concomitant treatments, per-treatment arising changes in physical examination, vital signs (blood pressure, pulse rate and body temperature), ECG, and clinical laboratory tests (biochemistry, haematology). Safety parameters will be graded based on NCI CTCAE v4.03 classification. The following parameters will be particulary followed: The incidence of haematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia); The incidence of GI toxicities, in particular diarrhea; The incidence of peripheral neuropathy.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Efficacy : 2 years from the date of randomization - Overall survival : the time from the date of randomization to the date of documented death from any cause
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 31 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 6 |