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

Sponsor
AIO-Studien-gGmbH (Other)
Overall Status
Terminated
CT.gov ID
NCT00889343
Collaborator
(none)
101
Enrollment
57
Locations
2
Arms
45
Duration (Months)
1.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Mar 1, 2009
Actual Primary Completion Date :
Nov 1, 2011
Actual Study Completion Date :
Dec 1, 2012

Arms and Interventions

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

    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

    Outcome Measures

    Primary Outcome Measures

    1. To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo [6 to 12 months]

    Secondary Outcome Measures

    1. Disease control rate [6 to 12 months]

    2. Overall survival [6 to 12 months]

    3. Response rates [6 to 12 months]

    4. Safety [signature of informed consent until 30 days after end of treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • AIO-Studien-gGmbH

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AIO-Studien-gGmbH
    ClinicalTrials.gov Identifier:
    NCT00889343
    Other Study ID Numbers:
    • AIO KRK 0307
    First Posted:
    Apr 28, 2009
    Last Update Posted:
    Mar 4, 2013
    Last Verified:
    Mar 1, 2013
    Keywords provided by AIO-Studien-gGmbH
    Second-line therapy of metastatic colorectal cancer
    Sorafenib
    Colorectal Neoplasms
    palliative therapy
    after progression of firstline therapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Leucovorin
    Fluorouracil
    Oxaliplatin
    Irinotecan
    Sorafenib

    Study Results

    No Results Posted as of Mar 4, 2013