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

Metastatic Colorectal Cancer Clinical Trial

— NEXIRI  

Official title:

SORAFENIB (NEXAVAR®) in Combination With Irinotecan in the Second Line Treatment or More of Metastatic Colorectal Cancer With K-RAS Mutation : a Multicentre Two-part Phase I/II Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989469
• Other study ID #: NEXIRI
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2009
• Est. completion date: February 2012

Study information

• Verified date: June 2021
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• 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

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille
France	Hopital Saint Eloi	Montpellier
France	Centre Rene Gauducheau	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHU Robert Debre	Reims

Sponsors (2)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease control		6 months
Secondary	Assessment of adverse events by using the NCI-CTCAE version 3 scale		6 months
Secondary	progression free survival		24 months
Secondary	overall survival		36 months