E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The primary objectif of the study is to increase by 15% the complete macroscopic resection rate of predominantly liver metastases from metastatic colorectal cancer through combining systemic cetuximab and hepatic artery infusion of three-drug chemotherapy
The primary end-point: incidence of complete macroscopic resections of liver metastases (R0+R1) |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to increase by 15% the complete macroscopic resection rate of predominantly liver metastases from metastatic colorectal cancer through combining systemic cetuximab and hepatic artery infusion of three-drug chemotherapy. Primary end-point: incidence of complete macroscopic resections of liver metastases (R0+R1).
|
|
E.2.2 | Secondary objectives of the trial |
Secondary end-points: • the rate of histologic complete responses, • the individual rates of R0 and R1 resections, • the rate and site(s) of relapse in the resected patients throughout the 3-year span that follows hepatectomy,, • the relapse-free survival curve and median in the resected patients, • the progression-free and the overall survival in the patients receiving at least 4 full courses of HAI therapy and in all the patients (intent to treat), • the objective response rate, • the rate of adverse events, • the dose intensities over 3, 6 and 9 courses, • the per-operative and post-operative complications associated to liver surgery. The study also includes a pharmacokinetic analysis, a translational research and a rest-activity monitoring investigation.
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The study also included a pharmacokinetic analysis, a translationnal research and a rest-activity monitoring investigation |
|
E.3 | Principal inclusion criteria |
•Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of liver metastases (new confirmation of metastatic disease is required in case the time interval from last histological diagnosis to enrolment exceeds 3 years). •Patient with wild type (WT) KRAS tumor status •Patient whose liver metastases are considered to be non resectable with curative intent in medico-surgical staff meeting. In particular patients with at least one of the following criteria, which prevent complete local treatment of liver metastasis with surgery alone or surgery plus radiofrequency ablation because: - less than 30% estimated residual liver after resection - disease in contact with liver main vessels - documented progressive disease on imaging documents or doubling of serum levels of carcino-embryonic antigen (CEA) or CA19.9 over the past 90 days or less •Patient with up to three resectable extrahepatic nodules of ≤ 10 mm •One, two or three prior chemotherapy lines for colorectal cancer •Written informed consent. •Age ³18 years. •Patient must be able to comply with the protocol. •Life expectancy of at least 3 months. •At least one measurable metastatic liver lesion (as per RECIST criteria). •WHO (World Health Organization) performance status of 0 or 1. •Adequate hematological function: absolute neutrophil count (ANC) ³1.0 x 109/L; platelets ³75 x 109/L, hemoglobin (Hb) ³8.5 g/dL. •International normalized ratio (INR) £1.5 and activated partial thromboplastin time (aPTT) £1.5 x upper limit of normal (ULN) within 7 days prior to starting study treatment, in the absence of any anticoagulant therapy. •Liver function: serum bilirubin £1.5 x ULN; alkaline phosphatase and transaminases <5 x ULN •Serum creatinine £ 1.5 x ULN. •Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).
|
|
E.4 | Principal exclusion criteria |
•Patient whose primary tumor or metastasis displays mutation of K-Ras (codon 12 and/or 13). •Unresectable extrahepatic diseases. •More than three resectable extrahepatic nodules. •Size of extra hepatic nodules > 1 cm •Prior HAI of the 3 drugs. •More than 2 prior surgical attempts for metastatic disease •Prior radiotherapy for metastatic disease. •WHO performance status ≥2 •Absolute neutrophil count (ANC) <1.0 x 109/L; platelets <75 x 109/L, hemoglobin (Hb) <8.5 g/dL. •serum bilirubin >1.5 x ULN; alkaline phosphatase and transaminases ≥5 x ULN •Serum creatinine > 1.5 x ULN. •Uncontrolled chronic inflammatory intestinal disease. •Known documented intolerance or hypersensitivity to any of the drugs used. •Sensory neuropathy grade 3 (National Cancer Institute-Common Terminology Criteria for Adverse Events -NCI-CTCAE, Version 3.0). •Past or current history (within the last 2 years prior to treatment start) of malignancy other than colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible). •Serious, non healing wound, ulcer, or bone fracture. •Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that puts the patient at high risk for treatment-related complications. •Pregnancy or lactation •Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception •Prior systemic administration of cetuximab or other anti-EGFR agent is not an exclusion criterion.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-point: incidence of complete macroscopic resection of liver metastases (R0+R1) |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 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 | 1 |
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 | 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
| |
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 |