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

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ClinicalTrials.gov Identifier: NCT01715441
Recruitment Status : Unknown
Verified March 2015 by Institut du Cancer de Montpellier - Val d'Aurelle.
Recruitment status was:  Recruiting
First Posted : October 29, 2012
Last Update Posted : March 3, 2015
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors Drug: Sorafenib and irinotecan combination Drug: Sorafenib monotherapy Drug: Irinotecan monotherapy Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2012
Estimated Primary Completion Date : March 2015
Estimated Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Non-progression rate [ Time Frame: At 2 months ]
    To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)

Secondary Outcome Measures :
  1. Disease control rate [ Time Frame: At 2 months ]
    According to RECIST criteria (Version 1.1)

  2. Treatment-related toxicity [ Time Frame: At 6 months ]
    According to NCI CTC V4.0

  3. 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.

  4. Quality of life [ Time Frame: 6 months ]
    Using the EORTC QLQ-C30 questionnaire

  5. 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.

  6. Response rate [ Time Frame: At 2 months ]
    According to RECIST criteria (Version 1.1)

Other Outcome Measures:
  1. Cmax and Tmax of sorafenib and irinotecan [ Time Frame: Up to 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

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 ClinicalTrials.gov identifier (NCT number): NCT01715441

Contact: Jean-Pierre Bleuse, MD 33 4 67 61 23 44 Jean-Pierre.Bleuse@montpellier.unicancer.fr

Hôpital AVICENNE Recruiting
Bobigny, France, 93009
Contact: Thomas APARICIO, MD       Thomas.aparicio@avc.aphp.fr   
Principal Investigator: Thomas APARICIO, MD         
Centre François Baclesse Recruiting
Caen, France, 14076
Contact: Marie-Pierre GALAIS, MD         
Principal Investigator: Marie-Pierre GALAIS, MD         
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Antoine ADENIS, MD       a-adenis@o-lambret.fr   
Principal Investigator: Antoine ADENIS, MD         
Centre Léon Bérard Recruiting
Lyon, France, 69373
Contact: Françoise DESSEIGNE, MD         
Principal Investigator: Françoise DESSEIGNE, MD         
Hôpital LA TIMONE Recruiting
Marseille, France, 13365
Contact: Jean-François SEITZ, MD       Jean-françois.seitz@ap-hm.fr   
Principal Investigator: Jean-François SEITZ, MD         
CRLC Val d'Aurelle-Paul Lamarque Recruiting
Montpellier, France, 34298
Contact: Emmanuelle SAMALIN, MD         
Principal Investigator: Emmanuelle SAMALIN, MD         
C.H.U. de REIMS Recruiting
Reims, France, 51092
Contact: Olivier BOUCHE, MD       Obouche@chu-reims.fr   
Principal Investigator: Olivier BOUCHE, MD         
CHU Charles Nicolle Recruiting
Rouen, France, 76038
Contact: Frédéric Di FIORE, MD    33    Frederic.Di-Fiore@chu-rouen.fr   
Principal Investigator: Frédéric Di FIORE, MD         
Institut de Cancérologie de l'Ouest - René Gauducheau Recruiting
St. Herblain, France, 44805
Contact: Jaafa BENNOUNA, MD       Jaafa.bennouna@ico.unicancer.fr   
Principal Investigator: Jaafa BENNOUNA, MD         
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Principal Investigator: Emmanuelle SAMALIN, MD CRLC Val d'Aurelle-Paul Lamarque
Study Chair: Marc YCHOU, MD, CRLC Val d'Aurelle

Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT01715441     History of Changes
Other Study ID Numbers: NEXIRI2
2012-000644-94 ( EudraCT Number )
First Posted: October 29, 2012    Key Record Dates
Last Update Posted: March 3, 2015
Last Verified: March 2015

Keywords provided by Institut du Cancer de Montpellier - Val d'Aurelle:
Metastatic colorectal cancer patients
KRAS mutation

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