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

NCT ID: NCT00989469

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-02-29

Brief 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sorafenib and irinotecan

Group Type: EXPERIMENTAL

Nexavar (Sorafenib) and irinotecan (Campto)

Intervention Type: DRUG

Sorafenib administrated continuously orally 400 mg twice daily (a daily total dose of 800 mg). Irinotecan 180 mg/m² will be administered IV for 90 minutes every 2 weeks. The first dose of sorafenib will be administered after the first perfusion of irinotecan 180 mg/m² at the first infusion

Interventions

Nexavar (Sorafenib) and irinotecan (Campto)

Sorafenib administrated continuously orally 400 mg twice daily (a daily total dose of 800 mg). Irinotecan 180 mg/m² will be administered IV for 90 minutes every 2 weeks. The first dose of sorafenib will be administered after the first perfusion of irinotecan 180 mg/m² at the first infusion

Intervention Type: DRUG

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 < 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmannuelle SAMALIN-SCALZI, Dr

Role: PRINCIPAL_INVESTIGATOR

CRLC Val d'Aurelle-Paul Lamarque

Locations

Centre Oscar Lambret

Lille, , France

Hopital Saint Eloi

Montpellier, , France

Centre Rene Gauducheau

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

CHU Robert Debre

Reims, , France

Countries

France

References

Samalin E, Bouche O, Thezenas S, Francois E, Adenis A, Bennouna J, Taieb J, Desseigne F, Seitz JF, Conroy T, Galais MP, Assenat E, Crapez E, Poujol S, Bibeau F, Boissiere F, Laurent-Puig P, Ychou M, Mazard T. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial. Br J Cancer. 2014 Mar 4;110(5):1148-54. doi: 10.1038/bjc.2013.813. Epub 2014 Jan 9.

Reference Type: RESULT

PMID: 24407191 (View on PubMed)

Other Identifiers

NEXIRI

Identifier Type: -

Identifier Source: org_study_id