A Trial to Assess Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors (NEXIRI 2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Centre Val d'Aurelle - Paul Lamarque
Sponsor:
Information provided by (Responsible Party):
Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier:
NCT01715441
First received: October 19, 2012
Last updated: February 4, 2014
Last verified: October 2012
  Purpose

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 Intervention 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
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Non-progression rate [ Time Frame: At 2 months ] [ Designated as safety issue: No ]
    To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)


Secondary Outcome Measures:
  • Disease control rate [ Time Frame: At 2 months ] [ Designated as safety issue: No ]
    According to RECIST criteria (Version 1.1)

  • Treatment-related toxicity [ Time Frame: At 6 months ] [ Designated as safety issue: Yes ]
    According to NCI CTC V4.0

  • Overall survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the date of inclusion to the date of death from any cause.

  • Quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Using the EORTC QLQ-C30 questionnaire

  • Progression Free Survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    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.

  • Response rate [ Time Frame: At 2 months ] [ Designated as safety issue: No ]
    According to RECIST criteria (Version 1.1)


Other Outcome Measures:
  • Cmax and Tmax of sorafenib and irinotecan [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: September 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT01715441

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

Locations
France
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 2.32.88.81.01    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
Centre Val d'Aurelle - Paul Lamarque
Investigators
Principal Investigator: Emmanuelle SAMALIN, MD CRLC Val d'Aurelle-Paul Lamarque
Study Chair: Marc YCHOU, MD, CRLC Val d'Aurelle
  More Information

No publications provided

Responsible Party: Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier: NCT01715441     History of Changes
Other Study ID Numbers: NEXIRI2, 2012-000644-94
Study First Received: October 19, 2012
Last Updated: February 4, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Val d'Aurelle - Paul Lamarque:
Metastatic colorectal cancer patients
KRAS mutation
Sorafenib

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

ClinicalTrials.gov processed this record on October 23, 2014