Metastatic Colorectal Cancer Patients With KRAS Mutated TumorsPhase 2NEXIRI2NCT01715441
Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors
A Phase 2 study testing Sorafenib and irinotecan combination, Sorafenib monotherapy and Irinotecan monotherapy in people with Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors, run by Institut du Cancer de Montpellier - Val d'Aurelle at 9 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors
- What is being tested?
- Sorafenib and irinotecan combination, Sorafenib monotherapy and Irinotecan monotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 173 participants
- Where
- 9 sitesFrance
- Study dates
- Sep 2012to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Hôpital AVICENNE
Bobigny, 93009
Centre François Baclesse
Caen, 14076
Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard
Lyon, 69373
Hôpital LA TIMONE
Marseille, 13365
CRLC Val d'Aurelle-Paul Lamarque
Montpellier, 34298
C.H.U. de REIMS
Reims, 51092
CHU Charles Nicolle
Rouen, 76038
Institut de Cancérologie de l'Ouest - René Gauducheau
Saint-Herblain, 44805
About this study
Official title: 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.
- Being tested
- Sorafenib and irinotecan combination, Sorafenib monotherapy, Irinotecan monotherapy
- Keywords
- Metastatic colorectal cancer patients, KRAS mutation, Sorafenib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib and irinotecan combinationDrug
Sorafenib monotherapyDrug
Irinotecan monotherapyDrug
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan monotherapy | Active comparator | Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression. Receives: Drug: Irinotecan monotherapy |
| Sorafenib monotherapy | Active comparator | Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression Receives: Drug: Sorafenib monotherapy |
| Sorafenib and irinotecan combination | Experimental | 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. Receives: Drug: Sorafenib and irinotecan combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-progression rate
To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)
Measured: At 2 months
Secondary outcomes (6)
Disease control rate
According to RECIST criteria (Version 1.1)
Measured: At 2 months
Treatment-related toxicity
According to NCI CTC V4.0
Measured: At 6 months
Overall survival
Overall survival is defined as the time from the date of inclusion to the date of death from any cause.
Measured: At 6 months
Quality of life questionnaire
Using the EORTC QLQ-C30 questionnaire
Measured: 6 months
Progression Free Survival
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.
Measured: At 6 months
Response rate
According to RECIST criteria (Version 1.1)
Measured: At 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study startSep 2012
- Primary completionMar 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal Cancer Patients With KRAS Mutated TumorsStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuelle SAMALIN, MD, Principal investigator, CRLC Val d'Aurelle-Paul LamarqueMarc YCHOU, MD,, Study chair, CRLC Val d'Aurelle
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01715441
- Sponsor's protocol ID
- NEXIRI2
- Other IDs
- 2012-000644-94
- Acronym
- NEXIRI2
- Status last verified
- Feb 2026
- First submitted
- 19 Oct 2012
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Samalin E, Fouchardiere C, Thezenas S, Boige V, Senellart H, Guimbaud R, Taieb J, Francois E, Galais MP, Lievre A, Seitz JF, Metges JP, Bouche O, Boissiere-Michot F, Lopez-Crapez E, Bibeau F, Ho-Pun-Cheung A, Ychou M, Adenis A, Di Fiore F, Mazard T. Sorafenib Plus Irinotecan Combination in Patients With RAS-mutated Metastatic Colorectal Cancer Refractory To Standard Combined Chemotherapies: A Multicenter, Randomized Phase 2 Trial (NEXIRI-2/PRODIGE 27). Clin Colorectal Cancer. 2020 Dec;19(4):301-310.e1. doi: 10.1016/j.clcc.2020.04.008. Epub 2020 May 15.
PubMed 32737004
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01715441
- Acronym / sponsor ID
- NEXIRI2 / NEXIRI2
- Keywords
- Metastatic colorectal cancer patients, KRAS mutation, Sorafenib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Study start
- Sep 2012 (actual)
- Primary completion
- Mar 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 29 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Irinotecan monotherapy | Active comparator | Drug: Irinotecan monotherapyIntravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression. |
| Sorafenib monotherapy | Active comparator | Drug: Sorafenib monotherapyOral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression |
| Sorafenib and irinotecan combination | Experimental | Drug: Sorafenib and irinotecan combinationIntravenous 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib and irinotecan combination | Drug | Sorafenib and irinotecan combination |
| Sorafenib monotherapy | Drug | Sorafenib monotherapy |
| Irinotecan monotherapy | Drug | Irinotecan monotherapy |
Primary outcome
Non-progression rate
Time frame: At 2 months
To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)
6 secondary outcomes
Disease control rate
Time frame: At 2 months
Treatment-related toxicity
Time frame: At 6 months
Overall survival
Time frame: At 6 months
Quality of life questionnaire
Time frame: 6 months
Progression Free Survival
Time frame: At 6 months
Response rate
Time frame: At 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Results publication: PubMed 32737004Samalin E, Fouchardiere C, Thezenas S, Boige V, Senellart H, Guimbaud R, Taieb J, Francois E, Galais MP, Lievre A, Seitz JF, Metges JP, Bouche O, Boissiere-Michot F, Lopez-Crapez E, Bibeau F, Ho-Pun-Cheung A, Ychou M, Adenis A, Di Fiore F, Mazard T. Sorafenib Plus Irinotecan Combination in Patients With RAS-mutated Metastatic Colorectal Cancer Refractory To Standard Combined Chemotherapies: A Multicenter, Randomized Phase 2 Trial (NEXIRI-2/PRODIGE 27). Clin Colorectal Cancer. 2020 Dec;19(4):301-310.e1. doi: 10.1016/j.clcc.2020.04.008. Epub 2020 May 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuelle SAMALIN, MD principal investigator
CRLC Val d'Aurelle-Paul Lamarque
Marc YCHOU, MD, study chair
CRLC Val d'Aurelle
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and irinotecan combination, Sorafenib monotherapy and Irinotecan monotherapy in people with Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors, run by Institut du Cancer de Montpellier - Val d'Aurelle at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-progression rate (time frame: At 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01715441, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.