E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
FULLY RESECTED STAGE III COLON CANCER |
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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 |
The primary objective of the study is to assess and to compare the disease free survival curves according to treatment arm in patients with completely resected stage III colon cancer and KRAS wild-type tumor status (ITT KRAS wild-type population).
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E.2.2 | Secondary objectives of the trial |
The secondary endpoints in the ITT KRAS wild-type population and all patients randomized until 17 June 2008 (modified ITT population, mITT) are: • Disease free survival (only for mITT) • 3-year disease-free survival • Overall survival • 5-year overall survival • 7-year overall survival • Treatment compliance • Identification of prognostic factors • Safety • Markers predictive for relapse and/or treatment efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with a KRAS wild-type tumor only (for patients to be enrolled after approval of amendment No. 3) - Inpatient or outpatient ≥ 18 and < 75 years of age - Pathologically confirmed stage III colon adenocarcinoma, regardless of the EGFR status - Curative R0 resection performed at least 28 days prior to start of study drug treatment and between 14 and 56 days prior to randomization. - No prior chemotherapy - No prior abdominal or pelvic irradiation - WHO performance status: 0 or 1 - Life expectancy of ≥ 5 years - Patients with childbearing potential should use effective contraception during the study and the following 6 months - White blood cell count ≥ 3 x 109/L with neutrophils ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL (5,6 mmol/l) - Total bilirubin ≤1.5 x ULN (upper limit of normal) - ASAT and ALAT ≤ 2.5 x ULN - Alkaline phosphatase ≤ 1.5 x ULN - Serum creatinine ≤ 1.5 x ULN - Carcinoembryogenic antigen (CEA) ≤ 1.5 x ULN after surgery (during screening period) - Signed written informed consent obtained prior to any study specific screening procedures
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E.4 | Principal exclusion criteria |
• 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 • Metastatic spread at baseline assessment • Rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery or having received radiation therapy prior to surgery • Presence of inflammatory bowel disease • Known hypersensitivity reaction to any of the components of study treatments • Pregnancy (absence to be confirmed by ß-hCG test) or breast-feeding period • Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia • Previous malignancy in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix • Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent • History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 • Any significant disease which, in the investigator’s opinion, would exclude the patient from the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary target variable is disease free survival (DFS). DFS is defined as the interval from randomization to locoregional or metastatic recurrence or the appearance of a secondary colorectal cancer or death, whichever occurs first. Patients who are alive and without recurrence or secondary colorectal cancer at the time of cut-off will be right-censored at the most recent date of assessment. Recurrence may be either histologically proven or evidenced by imaging. Isolated CEA elevation will not be sufficient to determine a relapse.
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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 | Yes |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 363 |
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 | Information not present in EudraCT |
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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The end of the study is defined as the day when all of the following requirements are fulfilled: •At least 30 days since last treatment of last patient under this study protocol •The trial is mature for final analysis of overall survival time •The database is fully cleaned and frozen for this final analysis of overall survival which is expected 10.5 years after study start
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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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial months | 6 |