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

Study Description

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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
Colorectal Neoplasms	Drug: Sorafenib; Drug: Placebo; Drug: Oxaliplatin or Irinotecan; Drug: Leucovorin; Drug: 5-Fluorouracil	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

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Study Type :	Interventional (Clinical Trial)
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 :	March 2009
Actual Primary Completion Date :	November 2011
Actual Study Completion Date :	December 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1	Drug: Sorafenib; 2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral; Other Name: 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

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Disease control rate [ Time Frame: 6 to 12 months ]
2. Overall survival [ Time Frame: 6 to 12 months ]
3. Response rates [ Time Frame: 6 to 12 months ]
4. Safety [ Time Frame: signature of informed consent until 30 days after end of treatment ]

Eligibility Criteria

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

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

AIO-Studien-gGmbH

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Arbeitsgemeinschaft der internistischen Onkologie 

Responsible Party:	AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:	NCT00889343 History of Changes
Other Study ID Numbers:	AIO KRK 0307
First Posted:	April 28, 2009
Last Update Posted:	March 4, 2013
Last Verified:	March 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; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Oxaliplatin; Irinotecan; Sorafenib; Fluorouracil	Niacinamide; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antimetabolites, Antineoplastic; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors; Vitamin B Complex; Vitamins