E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line treatment for epidermal growth factor receptor-expressing metastatic colorectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic colorectal cancer as first-line treatment |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
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 assess whether the progression-free survival time under 5-FU/FA plus irinotecan plus cetuximab is longer than that under 5-FU/FA plus irinotecan as first-line treatment for epidermal growth factor receptor-expressing metastatic colorectal cancer. |
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E.2.2 | Secondary objectives of the trial |
To compare between the 2 treatment groups for: Overall survival time Response rate (modified WHO criteria) Disease control rate To determine: Duration of response Quality of life (EORTC QLQ-C30 Questionnaire) Safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inpatient or outpatient ≥18 years of age Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum 1st occurrence of metastatic disease (not curatively resectable) Immunohistochemical evidence of epidermal growth factor receptor Expression in tumor tissue Life expectancy of at least 12 weeks Presence of at least 1 bi-dimensionally measurable index lesion (not lie in an irradiated area) ECOG performance status of ≤2 at study entry Effective contraception for both male and female patients if the risk of conception exists White blood cell count ≥3 x 10E9/L with neutrophils ≥1.5 x 10E9/L, platelet count ≥100 x 10E9/L, hemoglobin ≥5.6 mmol/L (9 g/dL) Total bilirubin ≤1.5 x upper reference range· AST ≤2.5 x upper reference range, or ≤5 x upper reference range in case of liver metastasis· Serum creatinine ≤1.5 x upper reference range· Recovery from relevant toxicity to previous treatment before study entry. |
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E.4 | Principal exclusion criteria |
Previous exposure to epidermal growth factor targeting therapy Previous irinotecan-based chemotherapy Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study Concurrent chronic systemic immune therapy or hormone therapy not indicated in this study protocol except for physiologic replacement Known hypersensitivity reaction to any of the components of study treatments· Pregnancy (absence to be confirmed by ß-hCG test) or lactation period Brain metastasis and leptomeningeal disease (known or suspected) Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia· Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analyses on PFS time will be conducted after the following 2 conditions have been met: 4 months have elapsed since the last patient was randomized and 633 patients have radiological evidence of PD. |
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E.5.2 | Secondary end point(s) |
Overall survival time • Best overall response • Duration of response • Disease control rate • Time to response • Quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints response rate, disease control rate, and duration of response will be conducted after the following 2 conditions have been met: 4 months have elapsed since the last patient was randomized and 633 patients have radiological evidence of PD. Final analyses of survival and safety will be conducted at the end of the study. |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 164 |
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 |
Argentina |
Australia |
Brazil |
Bulgaria |
Chile |
Hong Kong |
Israel |
Korea, Democratic People's Republic of |
Mexico |
Russian Federation |
Singapore |
South Africa |
Taiwan |
Ukraine |
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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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The end of trial will occur, when the following conditions are met: · The last patient received last dose of study treatment and · At least 705 events (deaths) have been observed and · A minimum follow-up of 40 days (five times the upper range of half-lives of cetuximab)
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 6 |