Clinical trial NCT00889343: Study to Evaluate the Effects of Sorafenib if Combined With Chemotherapy (FOLFOX6 or FOLFIRI) in the Second-Line Treatment of Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Keywords: 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
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
First posted: 2009-04-28
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo
timeFrame: 6 to 12 months
Secondary outcomes:
measure: Disease control rate
timeFrame: 6 to 12 months
measure: Overall survival
timeFrame: 6 to 12 months
measure: Response rates
timeFrame: 6 to 12 months
measure: Safety
timeFrame: signature of informed consent until 30 days after end of treatment
Other outcomes:
Locations:
city: Pforzheim
country: Germany
facility: Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum
state: Baden-Würtemberg
city: Aalen
country: Germany
facility: Ostalb-Klinikum Aalen, Medizinische Klinik 1
state: Baden-Württemberg
city: Nürtingen
country: Germany
facility: Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I
state: Baden-Württemberg
city: Ravensburg
country: Germany
facility: Gemeinschaftspraxis Onkologie Ravensburg
state: Baden-Württemberg
city: Singen
country: Germany
facility: Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I
state: Baden-Württemberg
city: Fürth
country: Germany
facility: Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner
state: Bayern
city: Herrsching
country: Germany
facility: Hämatologischonkologische Schwerpunktpraxis
state: Bayern
city: Landshut
country: Germany
facility: Hämatologie Onkologie Tagesklinik Landshut
state: Bayern
city: München
country: Germany
facility: Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller
state: Bayern
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus, Medizinische Klinik II
state: Bayern
city: Trostberg
country: Germany
facility: Kreiskliniken Traunstein -Trostberg GmbH , Innere Medizin/ Hämatologie und Onkologie
state: Bayern
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt, Medizinische Klinik V
state: Hessen
city: Frankfurt a.M.
country: Germany
facility: Städtische Kliniken Frankfurt a.M. - Höchst, Klinik für Innere Medizin Abt. 3
state: Hessen
city: Frankfurt
country: Germany
facility: Vitanus GmbH
state: Hessen
city: Fulda
country: Germany
facility: Klinikum Fulda, Tumorklinik
state: Hessen
city: Kassel
country: Germany
facility: Onkologische Praxisgemeinschaft Dres. Siehl, Söling und Prof. Hirschmann
state: Hessen
city: Marburg
country: Germany
facility: Philipps-Universität, Klinikum Marburg, Klinik für Innere Medizin mit SP Hämatologie und Onkologie
state: Hessen
city: Offenbach
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Internistische Onkologie
state: Hessen
city: Wetzlar
country: Germany
facility: Lahn-Dill-Kliniken GmbH, Darmzentrum
state: Hessen
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock, Klinik für Innere Medizin
state: Mecklenburg-Vorpommern
city: Rostock
country: Germany
facility: Wissenschaftskontor Nord GmbH und Co KG
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
facility: MediProjekt, Gesellschaft für Medizinstatistik und Projektentwicklung
state: Niedersachsen
city: Hannover
country: Germany
facility: Krankenhaus Siloah, Medizinische Klinik III
state: Niedersachsen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie
state: Niedersachsen
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis Hildesheim
state: Niedersachsen
city: Lehrte
country: Germany
facility: Hämatologie u. Internistische Onkologie
state: Niedersachsen
city: Northeim
country: Germany
facility: Hämatologisch-onkologische Schwerpunktpraxis Northeim
state: Niedersachsen
city: Osnabrück
country: Germany
facility: Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH,
state: Niedersachsen
city: Rotenburg (Wümme)
country: Germany
facility: Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, I. Chirurgische Klinik
state: Niedersachsen
city: Stade
country: Germany
facility: Praxisgemeinschaft Dr. Hancken und Partner, Onkologische Schwerpunktpraxis
state: Niedersachsen
city: Bochum
country: Germany
facility: Medizinische Universitätsklinik-Knappschaftskrankenhaus, Medizinische Klinik
state: Nordrhein-Westfalen
city: Datteln
country: Germany
facility: St. Vincenz-Krankenhaus, Medizinische Klinik I
state: Nordrhein-Westfalen
city: Eschweiler
country: Germany
facility: St. Antonius Hospital, Klinik für Hämatologie / Onkologie
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Hämato-Onkologisches Gemeinschaftspraxis
state: Nordrhein-Westfalen
city: Hagen
country: Germany
facility: Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und Onkologie
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie am Sachsenring
state: Nordrhein-Westfalen
city: Leverkusen
country: Germany
facility: Klinikum Leverkusen gGmbH, Medizinische Klinik III
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Gemeinschaftspraxis Hämatologie und Onkologie
state: Nordrhein-Westfalen
city: Recklinghausen
country: Germany
facility: Praxis und Tagesklinik für Internistische Onkologie und Hämatologie
state: Nordrhein-Westfalen
city: Recklinghausen
country: Germany
facility: Prosperhospital Recklinghausen, Medizinische Klinik I
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: Internistische Gemeinschaftspraxis
state: Nordrhein-Westfalen
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal , Medizinische Klinik I
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz
state: Rheinland-Pfalz
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen gGmbH, Innere Medizin I
state: Rheinland-Pfalz
city: Homburg / Saar
country: Germany
facility: Universitätskliniken des Saarlandes, Innere Medizin I
state: Saarland
city: Neunkirchen
country: Germany
facility: Hämatologisch-onkologische Praxis Dr. med. Peter Schmidt
state: Saarland
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau, Klinik für Innere Medizin
state: Sachsen-Anhalt
city: Halle (Saale)
country: Germany
facility: Onkologische Gemeinschaftspraxis
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Internistische Onkologie
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Praxisgemeinschaft Dr. med. Thomas Göhler und Steffen Dörfel
state: Sachsen
city: Neutstadt/Sachsen
country: Germany
facility: Internistische Praxis & Tagesklinik
state: Sachsen
city: Neumünster
country: Germany
facility: Friedrich-Ebert-Krankenhaus Neumünster, Klinik für Hämatologie, Onkologie und Nephrologie
state: Schleswig-Holstein
city: Jena
country: Germany
facility: eps-early phase solution GmbH
state: Thüringen
city: Weimar
country: Germany
facility: Sophien- und Hufeland-Klinikum gGmbH, Klinik für Innere Medizin II
state: Thüringen
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II
city: Hamburg
country: Germany
facility: MVZ für Innere Medizin in Hamburg Eppendorf
Study officials:
name: Thomas Höhler, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: