sorafenib with irinotecan in metastatic colorectal cancer (mcrc) and k-ras mutation

Conditions: Metastatic Colorectal Cancer

Summary: a multicentre two-part phase i/ii study evaluating response and safety of sorafenib in combination with irinotecan in the second line treatment or more of metastatic colorectal cancer with k-ras mutation.


Eligibility criteria:
inclusion criteria: * age \> 18 * written informed consent * histologically proven adenocarcinoma of the colon or rectum asymptomatic primary tumour or surgically removed mcrc patients with previously unresectable metastatic disease * patient with at least one tumoral lesion: measurable in a unidimensional way with a spiral scanner according to recist, no previous irradiation in this area * disease progression after irinotecan-based chemotherapy * disease progression after one or more previous lines of chemotherapy received in metastatic situation * who \<= 2 * patient having a mutated kras on 12 or 13 codons on the primary tumour or a metastasis * adequate liver function : bilirubin ≤ 1,5 x unl, asat ou alat ≤ 2,5 x unl (or \< 5 x unl for subjects having a hepatic insufficiency in connection with hepatic metastases) * polynuclear neutrophils ≥ 1 500/mm3 * haemoglobin \> 10g/dl * platelets ≥ 100 000/mm3 * amylase and lipase \< 1,5 x unl * serum creatinin \< 1,5 x unl * adapted contraceptive measures during treatment and continued at least three months after end of the treatment * life expectancy \> 3 months * affiliated to or benefiting from health insurance exclusion criteria: * gilbert's disease * brain metastases or carcinomatous symptomatic meningitis * exclusive bone metastasis * previous cancers not considered as cured in the 5 years before inclusion (except for baso-cellular skin carcinoma) surgery (except diagnostic biopsy) or radiotherapy within 4 weeks before inclusion * disorders of the cardiac rhythm requiring an anti-asynchronous treatment (except beta blockers or digoxine within the framework of a chronic auricular fibrillation), unstable coronaropathy or myocardial infarction \ rank ii nyha (grade 2), uncontrolled arterial hypertension * previous epilepsy crises requiring long term antiepileptic treatment previous organ transplant requiring immunosuppressor treatment severe bacterial or fungus infection (\> grade 2 nci ctc version 3) known hiv infection * long term treatment by known inductors of the cyp 3a4 like rifampicin, millepertuis (hypericum perforatum), phenytoin, carbamazepin, phenobarbital, dexamethasone et ketonazole * known allergy to one of the therapeutic agents * reasons (psychological, family, social or geographical) that could compromise the participation of the patient in the study * intestinal malabsorption or gastro-intestinal surgery being able to affect sorafenib absorption. occlusive or sub-occlusive syndrome. * dysphagic patient or patient not being able to take treatment by orally inflammatory * chronic digestive disease involving chronic diarrhoea (nci n+bethesda \>= 1.2g) * participation in another clinical trial within 30 days before the start of this study * other concomitant experimental drugs or other concomitant anticancer agents (except irinotecan and sorafenib) * medical or psychological state that in the opinion of the investigator will not allow the patient to terminate the study or to understand and sign the informed consent form * pregnancy and breast-feeding