E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Colorectal cancer KRAS wild-type |
|
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 |
This trial’s main objective is to assess the efficacy and safety of cetuximab plus FOLFOX in patients with advanced colorectal cancer that have progressed after 1st line treatment with cetuximab + FOLFIRI |
|
E.2.2 | Secondary objectives of the trial |
To assess the overall survival and time to disease progression in patients with advanced colorectal cancer, KRAS wild-type treated with cetuximab plus modified FOLFOX 6 versus modified FOLFOX 6 alone in patients who have progressed after a 1st line treatment with cetuximab + FOLFIRI.
To assess the combination safety profile. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed written informed consent - Male or Female with, at least, 18 years old - Histologically or cytologically-proven metastatic adenocarcinoma of the colon or rectum with wild-type KRAS status - Patients treated in 1st line treatment with cetuximab + FOLFIRI - Metastatic disease (M1) not amenable to potentially curative treatment - Presence of at least one unidimensionally measurable lesion with a diameter ≥ 20 mm by conventional CT or magnetic resonance imaging (MRI) or ≥ 10 mm by spiral CT (Target lesion(s) must not lie within an irradiated area) - Life expectancy of at least 3 months - ECOG performance status of 0 or 1 at study entry - Effective contraception for both male and female with reproductive potential while on treatment and for 6 months after study treatment |
|
E.4 | Principal exclusion criteria |
- Previous chemotherapy for 1st line metastatic CRC other than FOLFIRI + cetuximab - Brain metastases and/or leptomeningeal disease (known or suspected) - FOLFOX adjuvant treatment within 6 months prior to randomization - Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry. Prior radiotherapy is permitted if it was not administered to target lesions selected for this study - Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception - Patients that had stopped the 1st line cetuximab treatment for other reasons than PD or surgery for metastasis resection - Any concurrent malignancy other than non-melanoma cancer of the skin, or pre-invasive cancer of the cervix. (Patients with a previous malignancy but without evidence of disease for > 5 years will be allowed to enter the study). - Grade ≥ 2 neuropathy - Pregnancy (absence to be confirmed by beta-HCG test) or lactation period - Clinically relevant coronary artery disease or history of myocardial infarction in previous 12 months, or high risk of uncontrolled arrhythmia - Known drug abuse or alcohol abuse - Legal incapacity or limited legal capacity - Medical or psychological condition, which, in the opinion of the Investigator, would not permit the patient to complete the study or sign meaningful informed consent - Participation in another clinical study within 30 days before inclusion to this study - Significant disease which, in the Investigator's opinion, would exclude the patient from the study - Known hypersensitivity to any of the trial treatments |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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) | Yes |
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 | 13 |
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 | 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 | No |
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
|
The end of trial’s treatment period will be when all patients have progressed or withdrawn informed consent or have been withdrawn for toxicity reasons. After the end of the treatment period, survival and subsequent treatments will be assessed every three months for a 12 months period, beginning on the end of study date. This assessment will continue until 50% of the patients have died, in order to determine the median overall survival. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |