E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
resectable liver metastases of colorectal 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 objectives are to evaluate the safety and activity of the administration of an oxaliplatin-fluoropyrimidine regimen (modified FOLFOX6) in combination with either cetuximab alone or with cetuximab plus bevacizumab, as a pre- and post-operative treatment for resectable liver metastases from CRC The trial is a screening phase II trial with 2 investigational regimens. It is planned to further investigate the treatment(s) that are selected to be tolerable and active based on this phase II study in (a) future phase III trial(s) of the EORTC GI group focusing on resectable liver metastases of colorectal origin. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-male or female patients with potentially resectable liver metastases from CRC -patients with metachronous or synchronous metastases who have undergone comlete resection (R0) of the primary tumour at least 4 weeks before randomization into the study -no evidence of extra-hepatic disease -patients can be entered in the study irrespective of the EGFR-expression status of their CRC -WHO performance status: 0,1 -age: 18 to 80 years -no previous chemotherapy for metastatic disease -any previous adjuvant chemotherapy for primary cancer is allowed, except for patients who ended an oxaliplatin containing adjuvant treatment less than 12 months ago, and except for patients with persisting neuropathy -no previous exposure to EGFR- or VEGF/VEGFR-targeting therapy -absolute neutrophil count > 1.5 x 109 /L, platelets > 100 x 109/L, hemoglobin > 9 g/dL, and white blood cell count (WBC) > 3 x 109 /L -serum creatinine less than 1.5 times the upper limit of normal (ULN); no significant proteinuria (>500 mg/24 hours urine collection) -written informed consent before randomization according to ICH/EU GCP, and local, national and international regulations |
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E.4 | Principal exclusion criteria |
- major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to randomization - peripheral neuropathy and serious nonhealing wound, ulcer, or bone fracture - clinically significant cardiovascular disease - pregnancy or breast feeding. Adequate contraception is required for both male and female patienst if the risk of conception exists. Methods of adequate contraception are: condon use with spermicide, hormonal contraception, intra-uterine device - participation in another clinical study within the 30 days before randomization
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Response rate (pre-operative response rate) and safety (rate of peri-operative safety findings)
Seconday endpoints:
progression-free survival (PFS), pathological resection rate, and overall survival. |
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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 | No |
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 |
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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) | 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 | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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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End of study occurs when all of the following criteria have been satisfied: -thirty days have elapsed since all patients have stopped protocol treatment -the trial is mature for the analysis of the primary endpoint as defined in the protocol -the database has been fully cleaned and frozen for this analysis |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |