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

Phase 1

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Nexavar (Sorafenib) and irinotecan (Campto)

• Registration Number: NCT00989469
• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-10-02
• Study First Submitted QC: 2009-10-02
• Study First Posted: 2009-10-05
• Primary Completion: 2011-02
• Study Completion: 2012-02
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-17
• Last Update Posted: 2021-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib and irinotecan	Nexavar (Sorafenib) and irinotecan (Campto)	-

Primary Outcome Measures

Name	Time	Method
disease control	6 months

Secondary Outcome Measures

Name	Time	Method
Assessment of adverse events by using the NCI-CTCAE version 3 scale	6 months
progression free survival	24 months
overall survival	36 months

Trial Locations

Locations (5)

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Rene Gauducheau; 🇫🇷 Nantes, France

Hopital Saint Eloi; 🇫🇷 Montpellier, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CHU Robert Debre; 🇫🇷 Reims, France