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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Nexavar (Sorafenib) and irinotecan (Campto)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib and irinotecan<br> | Drug: Nexavar (Sorafenib) and irinotecan (Campto)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease control |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events by using the NCI-CTCAE version 3 scale |  | 6 months | 
| progression free survival |  | 24 months | 
| overall survival |  | 36 months |