Sorafenib With Irinotecan in Metastatic Colorectal Cancer (mCRC) and K-RAS Mutation

• Status: Completed
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Collaborator: Bayer
• Treatments: Camptothecin; Irinotecan; Niacinamide; Sorafenib

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 < 6 months, congestive cardiac failure > 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