Clinical trial NCT00989469: Sorafenib With Irinotecan in Metastatic Colorectal Cancer (mCRC) and K-RAS Mutation
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2009-10-05
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: disease control
timeFrame: 6 months
Secondary outcomes:
measure: Assessment of adverse events by using the NCI-CTCAE version 3 scale
timeFrame: 6 months
measure: progression free survival
timeFrame: 24 months
measure: overall survival
timeFrame: 36 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: Centre Rene Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Reims
country: France
facility: CHU Robert Debre
Study officials:
affiliation: CRLC Val d'Aurelle-Paul Lamarque
name: Emmannuelle SAMALIN-SCALZI, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.