Study to Evaluate the Effects of Sorafenib if Combined With Chemotherapy (FOLFOX6 or FOLFIRI) in the Second-Line Treatment of Colorectal Cancer

NCT ID: NCT00889343

Last Updated: 2013-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of this study is to determine whether sorafenib in combination with chemotherapy has a positive effect on time to progression of the tumor or death for the treatment of large bowel cancer that has already progressed during a first chemotherapy.

Detailed Description

Patients with metastatic CRC who received a first-line therapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab and had a progression subsequently, are eligible for this study. Patients will be randomized to receive chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib 400 mg bid or chemotherapy + placebo. Patients who have received an Oxaliplatin based Fluoropyrimidine containing regimen in first-line will obtain FOLFIRI during this study. Patients who have received an Irinotecan based Fluoropyrimidine containing regimen in first-line will obtain FOLFOX6.

Primary objective of the study is to compare the Progression-free-survival (PFS) between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo.

Conditions

Colorectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral

Oxaliplatin or Irinotecan

Intervention Type: DRUG

Oxaliplatin 100 mg/m2 intravenous infusion on day 1 of 14-days cycle, Irinotecan 180 mg/m2 intravenous infusion on day 1 of 14-days cycle

Leucovorin

Intervention Type: DRUG

400 mg/m2 intravenous infusion on day 1 of a 14-days cycle

5-Fluorouracil

Intervention Type: DRUG

400 mg/m2 intravenous bolus infusion on day 1, 2400 mg/m2 46 hour intravenous infusion on day 1 to 2 of a 14-days cycle

2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 filmcoated tablets BID, day 2-12 of a 14-days cycle, oral

Oxaliplatin or Irinotecan

Intervention Type: DRUG

Oxaliplatin 100 mg/m2 intravenous infusion on day 1 of 14-days cycle, Irinotecan 180 mg/m2 intravenous infusion on day 1 of 14-days cycle

Leucovorin

Intervention Type: DRUG

400 mg/m2 intravenous infusion on day 1 of a 14-days cycle

5-Fluorouracil

Intervention Type: DRUG

400 mg/m2 intravenous bolus infusion on day 1, 2400 mg/m2 46 hour intravenous infusion on day 1 to 2 of a 14-days cycle

Interventions

Sorafenib

2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral

Intervention Type: DRUG

Placebo

2 filmcoated tablets BID, day 2-12 of a 14-days cycle, oral

Intervention Type: DRUG

Oxaliplatin or Irinotecan

Oxaliplatin 100 mg/m2 intravenous infusion on day 1 of 14-days cycle, Irinotecan 180 mg/m2 intravenous infusion on day 1 of 14-days cycle

Intervention Type: DRUG

Leucovorin

400 mg/m2 intravenous infusion on day 1 of a 14-days cycle

Intervention Type: DRUG

5-Fluorouracil

400 mg/m2 intravenous bolus infusion on day 1, 2400 mg/m2 46 hour intravenous infusion on day 1 to 2 of a 14-days cycle

Intervention Type: DRUG

Other Intervention Names

Nexavar

Eligibility Criteria

Inclusion Criteria

• Age > 18 years.
• ECOG Performance Status of 0 to 2
• Life expectancy of at least 12 weeks.
• Subjects with at least one uni-dimensional (RECIST) measurable lesion of metastatic colorectal carcinoma after first-line chemotherapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab and had a progression subsequently. Lesions must be measured by CT-scan or MRI.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
• Hemoglobin > 9.0 g/dl
• Absolute neutrophil count (ANC) >1,500/mm3
• Platelet count 100,000/μl Total bilirubin < 1.5 times the upper limit of normal
• ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
• Alkaline phosphatase < 4 x upper limit of normal
• PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
• Serum creatinine < 1.5 x upper limit of normal
• Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria

• History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
• History of HIV infection or chronic hepatitis B or C
• Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
• Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Known deficit in Dihydropyrimidine Deshydrogenase (DPD)
• Contraindications for the use of atropine in patients receiving FOLFIRI
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
• Peripheral sensory neuropathy > CTC grade 2
• Chronic inflammatory bowel disease; ileus; genetic fructose intolerance
• Pregnant or breast-feeding patients.
• Women of childbearing potential must have a negative pregnancy test performed within 7 days before the start of treatment. Fertile women and men (<2 years after last menstruation in women) must use effective means of contraception (intrauterine contraceptive device, contraceptive implants, injectables (hormonal depot), transdermal hormonal contraception (contraceptive patch), sexual abstinence or vasectomised partner) during treatment and for at least 6 months after last administration of medication.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient"s participation in the study or evaluation of the study results
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 18. Patients unable to swallow oral medications.
• Any other anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
• Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study
• Autologous bone marrow transplant or stem cell rescue within 4 months prior to study treatment
• Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however, they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry
• Prior exposure to the study drug.
• Any St. John´s wort containing remedy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AIO-Studien-gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Höhler, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Locations

Ostalb-Klinikum Aalen, Medizinische Klinik 1

Aalen, Baden-Wurttemberg, Germany

Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I

Nürtingen, Baden-Wurttemberg, Germany

Gemeinschaftspraxis Onkologie Ravensburg

Ravensburg, Baden-Wurttemberg, Germany

Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz

Singen, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I

Ulm, Baden-Wurttemberg, Germany

Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum

Pforzheim, Baden-Würtemberg, Germany

Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner

Fürth, Bavaria, Germany

Hämatologischonkologische Schwerpunktpraxis

Herrsching am Ammersee, Bavaria, Germany

Hämatologie Onkologie Tagesklinik Landshut

Landshut, Bavaria, Germany

Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller

München, Bavaria, Germany

Leopoldina-Krankenhaus, Medizinische Klinik II

Schweinfurt, Bavaria, Germany

Kreiskliniken Traunstein -Trostberg GmbH , Innere Medizin/ Hämatologie und Onkologie

Trostberg an der Alz, Bavaria, Germany

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II

Bremen, City state Bremen, Germany

MVZ für Innere Medizin in Hamburg Eppendorf

Hamburg, City state of Hamburg, Germany

Klinikum Darmstadt, Medizinische Klinik V

Darmstadt, Hesse, Germany

Städtische Kliniken Frankfurt a.M. - Höchst, Klinik für Innere Medizin Abt. 3

Frankfurt a.M., Hesse, Germany

Vitanus GmbH

Frankfurt am Main, Hesse, Germany

Klinikum Fulda, Tumorklinik

Fulda, Hesse, Germany

Onkologische Praxisgemeinschaft Dres. Siehl, Söling und Prof. Hirschmann

Kassel, Hesse, Germany

Philipps-Universität, Klinikum Marburg, Klinik für Innere Medizin mit SP Hämatologie und Onkologie

Marburg, Hesse, Germany

Gemeinschaftspraxis für Hämatologie und Internistische Onkologie

Offenbach, Hesse, Germany

Lahn-Dill-Kliniken GmbH, Darmzentrum

Wetzlar, Hesse, Germany

MediProjekt, Gesellschaft für Medizinstatistik und Projektentwicklung

Hanover, Lower Saxony, Germany

Krankenhaus Siloah, Medizinische Klinik III

Hanover, Lower Saxony, Germany

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie

Hanover, Lower Saxony, Germany

Onkologische Schwerpunktpraxis Hildesheim

Hildesheim, Lower Saxony, Germany

Hämatologie u. Internistische Onkologie

Lehrte, Lower Saxony, Germany

Hämatologisch-onkologische Schwerpunktpraxis Northeim

Northeim, Lower Saxony, Germany

Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH,

Osnabrück, Lower Saxony, Germany

Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, I. Chirurgische Klinik

Rotenburg (Wümme), Lower Saxony, Germany

Praxisgemeinschaft Dr. Hancken und Partner, Onkologische Schwerpunktpraxis

Stade, Lower Saxony, Germany

Universitätsklinikum Rostock, Klinik für Innere Medizin

Rostock, Mecklenburg-Vorpommern, Germany

Wissenschaftskontor Nord GmbH und Co KG

Rostock, Mecklenburg-Vorpommern, Germany

Medizinische Universitätsklinik-Knappschaftskrankenhaus, Medizinische Klinik

Bochum, North Rhine-Westphalia, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie am Sachsenring

Cologne, North Rhine-Westphalia, Germany

St. Vincenz-Krankenhaus, Medizinische Klinik I

Datteln, North Rhine-Westphalia, Germany

St. Antonius Hospital, Klinik für Hämatologie / Onkologie

Eschweiler, North Rhine-Westphalia, Germany

Hämato-Onkologisches Gemeinschaftspraxis

Essen, North Rhine-Westphalia, Germany

Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und Onkologie

Hagen, North Rhine-Westphalia, Germany

Klinikum Leverkusen gGmbH, Medizinische Klinik III

Leverkusen, North Rhine-Westphalia, Germany

Gemeinschaftspraxis Hämatologie und Onkologie

Münster, North Rhine-Westphalia, Germany

Praxis und Tagesklinik für Internistische Onkologie und Hämatologie

Recklinghausen, North Rhine-Westphalia, Germany

Prosperhospital Recklinghausen, Medizinische Klinik I

Recklinghausen, North Rhine-Westphalia, Germany

Internistische Gemeinschaftspraxis

Witten, North Rhine-Westphalia, Germany

HELIOS Klinikum Wuppertal , Medizinische Klinik I

Wuppertal, North Rhine-Westphalia, Germany

I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH, Innere Medizin I

Trier, Rhineland-Palatinate, Germany

Universitätskliniken des Saarlandes, Innere Medizin I

Homburg / Saar, Saarland, Germany

Hämatologisch-onkologische Praxis Dr. med. Peter Schmidt

Neunkirchen, Saarland, Germany

Praxisgemeinschaft Dr. med. Thomas Göhler und Steffen Dörfel

Dresden, Saxony, Germany

Internistische Praxis & Tagesklinik

Neutstadt/Sachsen, Saxony, Germany

Städtisches Klinikum Dessau, Klinik für Innere Medizin

Dessau, Saxony-Anhalt, Germany

Onkologische Gemeinschaftspraxis

Halle, Saxony-Anhalt, Germany

Gemeinschaftspraxis für Hämatologie und Internistische Onkologie

Magdeburg, Saxony-Anhalt, Germany

Friedrich-Ebert-Krankenhaus Neumünster, Klinik für Hämatologie, Onkologie und Nephrologie

Neumünster, Schleswig-Holstein, Germany

eps-early phase solution GmbH

Jena, Thuringia, Germany

Sophien- und Hufeland-Klinikum gGmbH, Klinik für Innere Medizin II

Weimar, Thuringia, Germany

Countries

Germany

Related Links

http://www.aio-portal.de

Arbeitsgemeinschaft der internistischen Onkologie

Other Identifiers

AIO KRK 0307

Identifier Type: -

Identifier Source: org_study_id