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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00989469
Recruitment Status : Completed
First Posted : October 5, 2009
Last Update Posted : February 10, 2012
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Nexavar (Sorafenib) and irinotecan (Campto) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2009
Actual Primary Completion Date : February 2011
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Sorafenib and irinotecan 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

Primary Outcome Measures :
  1. disease control [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. toxicity [ Time Frame: 6 months ]
  2. progression free survival [ Time Frame: 24 months ]
  3. overall survival [ Time Frame: 36 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00989469

Centre Oscar Lambret
Lille, France
Hopital Saint Eloi
Montpellier, France
Centre Rene Gauducheau
Nantes, France
Centre Antoine Lacassagne
Nice, France
CHU Robert Debre
Reims, France
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Principal Investigator: Emmannuelle SAMALIN-SCALZI, Dr CRLC Val d'Aurelle-Paul Lamarque

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle Identifier: NCT00989469     History of Changes
Other Study ID Numbers: NEXIRI
First Posted: October 5, 2009    Key Record Dates
Last Update Posted: February 10, 2012
Last Verified: February 2012

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs