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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier:
NCT00989469
First received: October 2, 2009
Last updated: February 9, 2012
Last verified: February 2012
  Purpose

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 Intervention Phase
Metastatic Colorectal Cancer
Drug: Nexavar (Sorafenib) and irinotecan (Campto)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Centre Val d'Aurelle - Paul Lamarque:

Primary Outcome Measures:
  • disease control [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: February 2009
Study Completion Date: February 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989469

Locations
France
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
Centre Val d'Aurelle - Paul Lamarque
Bayer
Investigators
Principal Investigator: Emmannuelle SAMALIN-SCALZI, Dr CRLC Val d'Aurelle-Paul Lamarque
  More Information

No publications provided by Centre Val d'Aurelle - Paul Lamarque

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier: NCT00989469     History of Changes
Other Study ID Numbers: NEXIRI
Study First Received: October 2, 2009
Last Updated: February 9, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Sorafenib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014