Open-label, phase II, randomised, pilot study to evaluate the safety and efficacy of combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with EGFR-positive colorectal cancer (CRC) and exclusive non-resectable hepatic metastases
Conditions
Sponsors
Spanish Cooperative Group for Gastrointestinal Tomour therapy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent. - Men and women or= 4; 2.Size of one or more hepatic metastases > 5 cm diameter; 3. Vascular involvement and/or poor site that prevent complete resection of hepatic disease and/or require resection with the remaining liver mass less than 25-30% of functional liver. - Presence of at least one lesion detectable by two-dimensional measurement. - EGFR expression in primary tumour and/or at least one of the metastases demonstrated by immunohistochemical analysis prior to enrollment in study. - Karnofsky functional status >or=70% at the time of enrollment in study. - Life expectancy greater than 3 months. - Patients must not have received chemotherapy for advanced/metastatic disease. Patients with the following characteristics will be enrolled: 1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free period > 6 months following conclusion of treatment. 2. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment. 3. De novo diagnosis of disease. - Proper liver function, defined by aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) £ 2.5 x ULN (£ 5 x ULN if there are hepatic metastases) and total bilirubin count or = 1.5 x 109/l , platelets > or = 100 X 109/l and hemoglobin > or = 9 g/dl. - Effective birth control method for men as well as women if there is possibility of pregnancy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Documented or suspected cerebral and/or leptomeningeal metastases. - Metastasis in any other non-hepatic site, including extrahepatic lymph node metastases. - Surgery (excluding biopsy for diagnosis) and/or radiotherapy within 4 weeks prior to enrollment in the study. - Participation in another clinical trial with medication in the past 30 days. - Chronic, concomitant administration of systemic immunotherapy, chemotherapy, hormone therapy or any other investigational drug. - Prior malignant tumour in past 5 years, except history of basal cell skin carcinoma or pre-invasive cervical carcinoma. - Any investigational drug during the 4 weeks prior to enrolment. - Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment. - Prior participation in study in which treatment with cetuximab can be assigned (whether or not treatment with cetuximab is received). - Acute or subacute intestinal occlusion or history of inflammatory intestinal disease. - Evidence of grade 3 or 4 allergic reaction to any of the treatment components. - Clinically relevant peripheral neuropathy. - Clinically relevant myocardial disease or history of myocardial infarction in the past 12 months. - Known abuse of alcohol / drugs, Legal incapacity or limited legal capacity. - Any medical or psychological disorder which, in the opinion of the investigator, does not allow the patient to conclude the study or sign the informed consent. - Pregnant or nursing woman.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine confirmed objective response rate to combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with EGRF-positive CRC and non-resectable hepatic metastases;Secondary Objective: - Determine safety of combination - Determine surgical resectability and R0 resections in each study arm - Determine clinical benefit (complete and partial responses plus disease stabilisations) obtained in each study arm - Determine time to disease progression - Determine time to onset of response - Determine duration of response - Determine time to treatment failure - Determine overall survival time;Primary end point(s): Confirmed objective response rate to combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with EGRF-positive CRC and non-resectable hepatic metastases | — |
Countries
Spain
Outcome results
None listed