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

Institut du Cancer de Montpellier - Val d'Aurelle

Status and phase

Completed

Phase 2

Phase 1

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Nexavar (Sorafenib) and irinotecan (Campto)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00989469

NEXIRI

Details and patient eligibility

About

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.

Enrollment

64 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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