Sorafenib With Irinotecan in Metastatic Colorectal Cancer (mCRC) and K-RAS Mutation (NEXIRI)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Nexavar (Sorafenib) and irinotecan (Campto)
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
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
Sites / Locations
- Centre Oscar Lambret
- Hopital Saint Eloi
- Centre Rene Gauducheau
- Centre Antoine Lacassagne
- CHU Robert Debre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib and irinotecan
Arm Description
Outcomes
Primary Outcome Measures
disease control
Secondary Outcome Measures
Assessment of adverse events by using the NCI-CTCAE version 3 scale
progression free survival
overall survival
Full Information
NCT ID
NCT00989469
First Posted
October 2, 2009
Last Updated
June 17, 2021
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00989469
Brief Title
Sorafenib With Irinotecan in Metastatic Colorectal Cancer (mCRC) and K-RAS Mutation
Acronym
NEXIRI
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
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib and irinotecan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nexavar (Sorafenib) and irinotecan (Campto)
Intervention Description
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 Measure Information:
Title
disease control
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Assessment of adverse events by using the NCI-CTCAE version 3 scale
Time Frame
6 months
Title
progression free survival
Time Frame
24 months
Title
overall survival
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmannuelle SAMALIN-SCALZI, Dr
Organizational Affiliation
CRLC Val d'Aurelle-Paul Lamarque
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Facility Name
Hopital Saint Eloi
City
Montpellier
Country
France
Facility Name
Centre Rene Gauducheau
City
Nantes
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
CHU Robert Debre
City
Reims
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
24407191
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.
Results Reference
derived
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Sorafenib With Irinotecan in Metastatic Colorectal Cancer (mCRC) and K-RAS Mutation
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