Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors (NEXIRI2)

February 3, 2026 updated by: Institut du Cancer de Montpellier - Val d'Aurelle

A Randomized Phase II Trial Assessing Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors After Failure of All Drugs Known to be Effective

The aim of this multicenter randomized phase II trial is to determine the efficacy of sorafenib and irinotecan combination versus irinotecan monotherapy or versus sorafenib monotherapy in metastatic colorectal cancer patients with KRAS mutated tumors after failure of all active drugs known to be effective.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
173

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bobigny, France, 93009
        • Hopital Avicenne
      • Caen, France, 14076
        • Centre Francois Baclesse
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13365
        • Hôpital La Timone
      • Montpellier, France, 34298
        • CRLC Val d'Aurelle-Paul Lamarque
      • Reims, France, 51092
        • C.H.U. de REIMS
      • Rouen, France, 76038
        • CHU Charles Nicolle
      • Saint-Herblain, France, 44805
        • Institut de cancérologie de l'Ouest - René Gauducheau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female ≥ 18 years old
  • Histologically confirmed diagnosis of colorectal cancer
  • Asymptomatic or resected primary tumor
  • Metastatic colorectal cancer patient not eligible for curative surgery

  • At least one target lesion:

    • Unidimensionally measurable on cross-sectional imaging
    • In an area not previously irradiated
  • Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan, oxaliplatin, bevacizumab)
  • Patients with bone metastases are eligible if they have other measurable lesions
  • WHO performance status ≤ 2
  • Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases
  • Total bilirubin ≤ 1.5 ULN, ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
  • Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3
  • Serum creatinine ≤ 1.5 ULN
  • Negative pregnancy test in women of childbearing potential
  • Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment in males and females
  • Life expectancy of at least 3 months
  • Informed consent signed prior any study specific procedures
  • Tumor evaluation should be performed within 3 weeks prior to starting treatment

Exclusion Criteria:

  • History of Gilbert's syndrome
  • Symptomatic brain metastases or carcinomatous meningitis
  • Bone-only metastases
  • History or presence of other cancers within the past 5 years (except curatively treated non-melanoma skin cancer and in situ cervical cancer)
  • Prior surgery or radiotherapy within 4 weeks before entering the study
  • Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin), unstable cardiac disease, myocardial infarction within the previous 6 months, > grade II NYHA heart failure, uncontrolled hypertension
  • Kalemia lower than normal serum potassium value
  • From ECG, QTc interval > 470 ms
  • History of acute or chronic pancreatitis
  • History of epileptic seizures requiring long-term anticonvulsant therapy
  • History of organ transplantation with use of immunosuppression therapy
  • Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.4.0)
  • Known HIV infection
  • Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and ketoconazole
  • Pregnant or breastfeeding women
  • Bowel malabsorption or extended bowel resection that could affect the absorption of sorafenib, occlusive syndrome, inability to take oral medications
  • Inflammatory bowel disease with chronic diarrhea (NCI-CTCAE v.4.0)
  • Participation in another clinical trial 30 days prior to study entry
  • Concurrent treatment with any other investigational product or anticancer therapy (except for irinotecan or sorafenib)
  • Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Irinotecan monotherapy
Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression.
Drug: Irinotecan monotherapy
Active Comparator: Sorafenib monotherapy
Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression
Drug: Sorafenib monotherapy
Experimental: Sorafenib and irinotecan combination

Intravenous infusion irinotecan 120 mg/m2 over 90 minutes (D1=D15) at Cycle 1, 150 mg/m² at C2 if no diarrhea > grade 1 and no other toxicity > grade 2, and 180 mg/m² at C3 in the same conditions

  • Oral sorafenib 400 mg twice daily (total dose 800 mg/day) from C1. 1 cycle = 15 days and 1 course = 4 weeks.
Drug: Sorafenib and irinotecan combination

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Non-progression rate
Time Frame: At 2 months
To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)
At 2 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease control rate
Time Frame: At 2 months
According to RECIST criteria (Version 1.1)
At 2 months
Treatment-related toxicity
Time Frame: At 6 months
According to NCI CTC V4.0
At 6 months
Overall survival
Time Frame: At 6 months
Overall survival is defined as the time from the date of inclusion to the date of death from any cause.
At 6 months
Quality of life questionnaire
Time Frame: 6 months
Using the EORTC QLQ-C30 questionnaire
6 months
Progression Free Survival
Time Frame: At 6 months
Progression Free Survival is defined as the time from the date of inclusion to first documentation of objective tumor progression or to death due to progression.
At 6 months
Response rate
Time Frame: At 2 months
According to RECIST criteria (Version 1.1)
At 2 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Cmax and Tmax of sorafenib and irinotecan
Time Frame: Up to 3 months
Up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Emmanuelle SAMALIN, MD, CRLC Val d'Aurelle-Paul Lamarque
  • Study Chair: Marc YCHOU, MD,, CRLC Val d'Aurelle

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 29, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NEXIRI2
  • 2012-000644-94 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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