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

March 1, 2013 updated by: AIO-Studien-gGmbH

A Controlled Randomized Double-blind Multi-center Phase II Study of FOLFOX6 or FOLFIRI Combined With Sorafenib Versus Placebo in Second-line Metastatic Colorectal Carcinoma

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • 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

  • Germany
      • Bremen, Germany, 28239
        • DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II
      • Hamburg, Germany, 20248
        • MVZ für Innere Medizin in Hamburg Eppendorf
    • Baden-Würtemberg
      • Pforzheim, Baden-Würtemberg, Germany, 75179
        • Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum
    • Baden-Württemberg
      • Aalen, Baden-Württemberg, Germany, 73428
        • Ostalb-Klinikum Aalen, Medizinische Klinik 1
      • Nürtingen, Baden-Württemberg, Germany, 72622
        • Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I
      • Ravensburg, Baden-Württemberg, Germany, 88214
        • Gemeinschaftspraxis Onkologie Ravensburg
      • Singen, Baden-Württemberg, Germany, 78224
        • Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz
      • Ulm, Baden-Württemberg, Germany, 89070
        • Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I
    • Bayern
      • Fürth, Bayern, Germany, 90766
        • Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner
      • Herrsching, Bayern, Germany, 82211
        • Hämatologischonkologische Schwerpunktpraxis
      • Landshut, Bayern, Germany, 84028
        • Hämatologie Onkologie Tagesklinik Landshut
      • München, Bayern, Germany, 80639
        • Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller
      • Schweinfurt, Bayern, Germany, 97422
        • Leopoldina-Krankenhaus, Medizinische Klinik II
      • Trostberg, Bayern, Germany, 83308
        • Kreiskliniken Traunstein -Trostberg GmbH , Innere Medizin/ Hämatologie und Onkologie
    • Hessen
      • Darmstadt, Hessen, Germany, 64283
        • Klinikum Darmstadt, Medizinische Klinik V
      • Frankfurt, Hessen, Germany, 60596
        • Vitanus GmbH
      • Frankfurt a.M., Hessen, Germany, 65929
        • Städtische Kliniken Frankfurt a.M. - Höchst, Klinik für Innere Medizin Abt. 3
      • Fulda, Hessen, Germany, 36043
        • Klinikum Fulda, Tumorklinik
      • Kassel, Hessen, Germany, 34117
        • Onkologische Praxisgemeinschaft Dres. Siehl, Söling und Prof. Hirschmann
      • Marburg, Hessen, Germany, 35043
        • Philipps-Universität, Klinikum Marburg, Klinik für Innere Medizin mit SP Hämatologie und Onkologie
      • Offenbach, Hessen, Germany, 63065
        • Gemeinschaftspraxis für Hämatologie und internistische Onkologie
      • Wetzlar, Hessen, Germany, 35578
        • Lahn-Dill-Kliniken GmbH, Darmzentrum
    • Mecklenburg-Vorpommern
      • Rostock, Mecklenburg-Vorpommern, Germany, 18057
        • Universitätsklinikum Rostock, Klinik für Innere Medizin
      • Rostock, Mecklenburg-Vorpommern, Germany, 18107
        • Wissenschaftskontor Nord GmbH und Co KG
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30171
        • Mediprojekt, Gesellschaft für Medizinstatistik und Projektentwicklung
      • Hannover, Niedersachsen, Germany, 30449
        • Krankenhaus Siloah, Medizinische Klinik III
      • Hannover, Niedersachsen, Germany, 30625
        • Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie
      • Hildesheim, Niedersachsen, Germany, 31135
        • Onkologische Schwerpunktpraxis Hildesheim
      • Lehrte, Niedersachsen, Germany, 31275
        • Hämatologie u. Internistische Onkologie
      • Northeim, Niedersachsen, Germany, 37154
        • Hämatologisch-onkologische Schwerpunktpraxis Northeim
      • Osnabrück, Niedersachsen, Germany, 49074
        • Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH,
      • Rotenburg (Wümme), Niedersachsen, Germany, 27356
        • Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, I. Chirurgische Klinik
      • Stade, Niedersachsen, Germany, 21680
        • Praxisgemeinschaft Dr. Hancken und Partner, Onkologische Schwerpunktpraxis
    • Nordrhein-Westfalen
      • Bochum, Nordrhein-Westfalen, Germany, 44892
        • Medizinische Universitätsklinik-Knappschaftskrankenhaus, Medizinische Klinik
      • Datteln, Nordrhein-Westfalen, Germany, 45711
        • St. Vincenz-Krankenhaus, Medizinische Klinik I
      • Eschweiler, Nordrhein-Westfalen, Germany, 52249
        • St. Antonius Hospital, Klinik für Hämatologie / Onkologie
      • Essen, Nordrhein-Westfalen, Germany, 45136
        • Hämato-Onkologisches Gemeinschaftspraxis
      • Hagen, Nordrhein-Westfalen, Germany, 58095
        • Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und Onkologie
      • Köln, Nordrhein-Westfalen, Germany, 50677
        • Gemeinschaftspraxis für Hämatologie und Onkologie am Sachsenring
      • Leverkusen, Nordrhein-Westfalen, Germany, 51375
        • Klinikum Leverkusen gGmbH, Medizinische Klinik III
      • Münster, Nordrhein-Westfalen, Germany, 48149
        • Gemeinschaftspraxis Hämatologie und Onkologie
      • Recklinghausen, Nordrhein-Westfalen, Germany, 45657
        • Praxis und Tagesklinik für Internistische Onkologie und Hämatologie
      • Recklinghausen, Nordrhein-Westfalen, Germany, 45659
        • Prosperhospital Recklinghausen, Medizinische Klinik I
      • Witten, Nordrhein-Westfalen, Germany, 58452
        • Internistische Gemeinschaftspraxis
      • Wuppertal, Nordrhein-Westfalen, Germany, 42283
        • HELIOS Klinikum Wuppertal , Medizinische Klinik I
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany, 55131
        • I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz
      • Trier, Rheinland-Pfalz, Germany, 54290
        • Klinikum Mutterhaus der Borromäerinnen gGmbH, Innere Medizin I
    • Saarland
      • Homburg / Saar, Saarland, Germany, 66421
        • Universitätskliniken des Saarlandes, Innere Medizin I
      • Neunkirchen, Saarland, Germany, 66821
        • Hämatologisch-onkologische Praxis Dr. med. Peter Schmidt
    • Sachsen
      • Dresden, Sachsen, Germany, 01127
        • Praxisgemeinschaft Dr. med. Thomas Göhler und Steffen Dörfel
      • Neutstadt/Sachsen, Sachsen, Germany, 01844
        • Internistische Praxis & Tagesklinik
    • Sachsen-Anhalt
      • Dessau, Sachsen-Anhalt, Germany, 06847
        • Städtisches Klinikum Dessau, Klinik für Innere Medizin
      • Halle (Saale), Sachsen-Anhalt, Germany, 06110
        • Onkologische Gemeinschaftspraxis
      • Magdeburg, Sachsen-Anhalt, Germany, 39104
        • Gemeinschaftspraxis für Hämatologie und internistische Onkologie
    • Schleswig-Holstein
      • Neumünster, Schleswig-Holstein, Germany, 24534
        • Friedrich-Ebert-Krankenhaus Neumünster, Klinik für Hämatologie, Onkologie und Nephrologie
    • Thüringen
      • Jena, Thüringen, Germany, 07743
        • eps-early phase solution GmbH
      • Weimar, Thüringen, Germany, 99425
        • Sophien- und Hufeland-Klinikum gGmbH, Klinik für Innere Medizin II

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Drug: Sorafenib
2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral
Other Names:
  • Nexavar
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
Drug: Leucovorin
400 mg/m2 intravenous infusion on day 1 of a 14-days cycle
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
Placebo Comparator: 2
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
Drug: Leucovorin
400 mg/m2 intravenous infusion on day 1 of a 14-days cycle
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
Drug: Placebo
2 filmcoated tablets BID, day 2-12 of a 14-days cycle, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo
Time Frame: 6 to 12 months
6 to 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease control rate
Time Frame: 6 to 12 months
6 to 12 months
Overall survival
Time Frame: 6 to 12 months
6 to 12 months
Response rates
Time Frame: 6 to 12 months
6 to 12 months
Safety
Time Frame: signature of informed consent until 30 days after end of treatment
signature of informed consent until 30 days after end of treatment

Collaborators and Investigators

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

Sponsor

AIO-Studien-gGmbH

Investigators

  • Principal Investigator: Thomas Höhler, Prof. Dr. med.

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.

Helpful Links

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

March 1, 2009

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

April 17, 2009

First Submitted That Met QC Criteria

April 27, 2009

First Posted (Estimate)

April 28, 2009

Study Record Updates

Last Update Posted (Estimate)

March 4, 2013

Last Update Submitted That Met QC Criteria

March 1, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIO KRK 0307

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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