E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
first-line therapy in patients with metastatic colorectal cancer |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 |
To assess the efficacy of FOLFOX4 plus weekly cetuximab and FOLFOX4 plus cetuximab every two weeks with respect to the objective response rates as assessed by RECIST criteria, in each arm. |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of both regimens with respect to the percentage of patients surviving without disease progression as assessed by RECIST criteria in each arm, and the overall survival in each arm.
To evaluate the safety profile of these combinations by recording the adverse events and abnormal laboratory values associated with the study treatments.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed written informed consent • Male or female at least 18 years of age • Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum • Metastatic colorectal carcinoma not suitable for curative-intent resection • Availability of tumor sample (or able and willing to provide tumor sample) for EGFR assessment • Presence of at least one lesion measurable unidimensionally by CT scan or MRI (target lesion(s) must not lie within an irradiated area) • Karnofsky performance status of > 80 at study entry • Leucocytes at least 3.0 x 109/L and neutrophils at least 1.5 x 109/L, platelets at least 100 x 109/L, and hemoglobin at least 9 g/dL • Bilirubin not exceeding 1.5 x ULN • ASAT and ALAT not exceeding 2.5 x ULN (not exceeding 5 x ULN if liver metastasis are present) • Serum creatinine not exceeding 1.5 x ULN
|
|
E.4 | Principal exclusion criteria |
• Brain metastasis (known or suspected) • Previous chemotherapy for metastatic disease. Prior adjuvant chemotherapy is allowed if the chemotherapy treatment free interval is > 6 months. • Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol • Any investigational agent(s) within 4 weeks prior to entry • Previous exposure to EGFR-pathway targeting therapy • Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months • Acute or subacute intestinal occlusion or history of inflammatory bowel disease • Pre-existing neuropathy > grade 1. In case of prior oxaliplatin containing adjuvant chemotherapy: pre-existing neuropathy of grade 1 or higher. • Known grade 3 or 4 allergic reaction to any of the components of the treatment. • Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for at least 5 years will be allowed to enter the trial) • Pregnancy or lactation • Inadequate contraception (male or female patients) if of childbearing or procreational potential • 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 patient to complete the study or sign meaningful informed consent
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response (CR/PR), as assessed by RECIST criteria |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
same product with different dosing and administration schedule |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 study is defined as the day when all of the following requirements are fulfilled: • At least 6 weeks since last treatment of any 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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |