Metastatic Colorectal Cancer
Conditions
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.
Interventions
DRUGNexavar (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
Sponsors
Institut du Cancer de Montpellier - Val d'Aurelle
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| disease control | 6 months |
Secondary
| Measure | 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 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATOREmmannuelle SAMALIN-SCALZI, Dr
CRLC Val d'Aurelle-Paul Lamarque
Outcome results
None listed