E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Metastatic colorectal cancer | |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 | E.1.2 | Level | LLT | E.1.2 | Classification code | 10052362 | E.1.2 | Term | Metastatic colorectal cancer | |
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 this study is to compare the PFS in subjects receiving cetuximab plus either UFOX or FOLFOX-4 as initial treatment for metastatic colorectal cancer. | |
E.2.2 | Secondary objectives of the trial | The secondary objectives of this study include the assessment and comparison of: •Response rate (the sum of CR rate and PR rate) in each treatment group •OS in each treatment group •Safety •Quality of Life (QOL), assessed by Functional Assessment of Cancer Therapy–Colorectal (FACT-C), and Euro-QOL (EQ-5D) at each site where appropriate translations of the questionnaires are available and validated, as well as the Therapy Preference Questionnaire (TPQ) •Treatment impact on social daily living and health care resource utilization | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | Both male and female subjects are eligible for randomization. For inclusion in the study, all of the following inclusion criteria must be fulfilled: •Subject has given written informed consent before any study-related activities are carried out •Inpatient or outpatient ≥18 years of age •Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum •First occurrence of metastatic disease (at presentation not curatively resectable) •Presence of at least one lesion unidimensionally measurable by CT- and/or MRI-scans. (target lesion(s) must not lie within an irradiated area) •Life expectancy of ≥3 months •Karnofsky performance status of ≥60 at study entry •White blood cell count (WBC) ≥3 x 10^9/L, with neutrophils ≥1.5 x 10^9/L, platelets ≥100 x 10^9/L, and hemoglobin ≥9 g/dL •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal range (ULN) (<5 x ULN if liver metastasis are present) •Normal serum creatinine (in case of elevated creatinine, labeled EDTA (ethylenediaminetetraacetic acid) clearance ≥65mL/min is acceptable) •Effective contraception for both male and female subjects if the risk of conception exists •Tumor biopsy or archived tumor sample available | |
E.4 | Principal exclusion criteria | Subjects are not eligible for this study if they fulfill one or more of the following exclusion criteria: •Brain metastasis and/or leptomeningeal disease (known or suspected) •Previous chemotherapy for CRC except adjuvant treatment with progression of disease documented >6 months after end of adjuvant treatment •Previous oxaliplatin-based chemotherapy •Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to randomization •Concurrent or previous chronic systemic immune therapy, targeted therapy, anti-VEGF therapy, or EGFR-pathway targeting therapy not indicated in the study protocol •Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception •Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia •Peripheral neuropathy >grade 1 •Known hypersensitivity reaction to any of the components of the treatment •Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive cancer of the cervix (subjects with a previous malignancy but without evidence of disease for ≥5 years will be allowed to enter the study) •Pregnancy (absence to be confirmed by beta-human choriongonadotrophin [β-hCG] test) or lactation period •Known drug abuse/alcohol abuse •Legal incapacity or limited legal capacity •Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent •Participation in another clinical study within the 30 days before randomization •Significant disease which, in the investigator’s opinion, would exclude the subject from the study | |
E.5 End points |
E.5.1 | Primary end point(s) | The primary variable is progression-free survival. | |
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 | Yes |
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 | Yes |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 | Information not present in EudraCT |
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 | |
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 the trial occurs 12 months after all subjects have completed the end of study visit. | |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |