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

Colorectal Neoplasms Clinical Trial

— FOSCO  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00889343
• Other study ID #: AIO KRK 0307
• Status: Terminated
• Phase: Phase 2
• First received: April 17, 2009
• Last updated: March 1, 2013
• Start date: March 2009
• Est. completion date: December 2012

Study information

• Verified date: March 2013
• Source: AIO-Studien-gGmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 101
• Est. completion date: December 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Sorafenib
2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral
• Placebo
2 filmcoated tablets BID, day 2-12 of a 14-days cycle, oral
• 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
• Leucovorin
400 mg/m2 intravenous infusion on day 1 of a 14-days cycle
• 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

Locations

Country	Name	City	State
Germany	Ostalb-Klinikum Aalen, Medizinische Klinik 1	Aalen	Baden-Württemberg
Germany	Medizinische Universitätsklinik-Knappschaftskrankenhaus, Medizinische Klinik	Bochum	Nordrhein-Westfalen
Germany	DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II	Bremen
Germany	Klinikum Darmstadt, Medizinische Klinik V	Darmstadt	Hessen
Germany	St. Vincenz-Krankenhaus, Medizinische Klinik I	Datteln	Nordrhein-Westfalen
Germany	Städtisches Klinikum Dessau, Klinik für Innere Medizin	Dessau	Sachsen-Anhalt
Germany	Praxisgemeinschaft Dr. med. Thomas Göhler und Steffen Dörfel	Dresden	Sachsen
Germany	St. Antonius Hospital, Klinik für Hämatologie / Onkologie	Eschweiler	Nordrhein-Westfalen
Germany	Hämato-Onkologisches Gemeinschaftspraxis	Essen	Nordrhein-Westfalen
Germany	Vitanus GmbH	Frankfurt	Hessen
Germany	Städtische Kliniken Frankfurt a.M. - Höchst, Klinik für Innere Medizin Abt. 3	Frankfurt a.M.	Hessen
Germany	Klinikum Fulda, Tumorklinik	Fulda	Hessen
Germany	Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner	Fürth	Bayern
Germany	Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und Onkologie	Hagen	Nordrhein-Westfalen
Germany	Onkologische Gemeinschaftspraxis	Halle (Saale)	Sachsen-Anhalt
Germany	MVZ für Innere Medizin in Hamburg Eppendorf	Hamburg
Germany	Krankenhaus Siloah, Medizinische Klinik III	Hannover	Niedersachsen
Germany	MediProjekt, Gesellschaft für Medizinstatistik und Projektentwicklung	Hannover	Niedersachsen
Germany	Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie	Hannover	Niedersachsen
Germany	Hämatologischonkologische Schwerpunktpraxis	Herrsching	Bayern
Germany	Onkologische Schwerpunktpraxis Hildesheim	Hildesheim	Niedersachsen
Germany	Universitätskliniken des Saarlandes, Innere Medizin I	Homburg / Saar	Saarland
Germany	eps-early phase solution GmbH	Jena	Thüringen
Germany	Onkologische Praxisgemeinschaft Dres. Siehl, Söling und Prof. Hirschmann	Kassel	Hessen
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie am Sachsenring	Köln	Nordrhein-Westfalen
Germany	Hämatologie Onkologie Tagesklinik Landshut	Landshut	Bayern
Germany	Hämatologie u. Internistische Onkologie	Lehrte	Niedersachsen
Germany	Klinikum Leverkusen gGmbH, Medizinische Klinik III	Leverkusen	Nordrhein-Westfalen
Germany	Gemeinschaftspraxis für Hämatologie und Internistische Onkologie	Magdeburg	Sachsen-Anhalt
Germany	I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Philipps-Universität, Klinikum Marburg, Klinik für Innere Medizin mit SP Hämatologie und Onkologie	Marburg	Hessen
Germany	Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller	München	Bayern
Germany	Gemeinschaftspraxis Hämatologie und Onkologie	Münster	Nordrhein-Westfalen
Germany	Friedrich-Ebert-Krankenhaus Neumünster, Klinik für Hämatologie, Onkologie und Nephrologie	Neumünster	Schleswig-Holstein
Germany	Hämatologisch-onkologische Praxis Dr. med. Peter Schmidt	Neunkirchen	Saarland
Germany	Internistische Praxis & Tagesklinik	Neutstadt/Sachsen	Sachsen
Germany	Hämatologisch-onkologische Schwerpunktpraxis Northeim	Northeim	Niedersachsen
Germany	Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I	Nürtingen	Baden-Württemberg
Germany	Gemeinschaftspraxis für Hämatologie und Internistische Onkologie	Offenbach	Hessen
Germany	Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH,	Osnabrück	Niedersachsen
Germany	Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum	Pforzheim	Baden-Würtemberg
Germany	Gemeinschaftspraxis Onkologie Ravensburg	Ravensburg	Baden-Württemberg
Germany	Praxis und Tagesklinik für Internistische Onkologie und Hämatologie	Recklinghausen	Nordrhein-Westfalen
Germany	Prosperhospital Recklinghausen, Medizinische Klinik I	Recklinghausen	Nordrhein-Westfalen
Germany	Universitätsklinikum Rostock, Klinik für Innere Medizin	Rostock	Mecklenburg-Vorpommern
Germany	Wissenschaftskontor Nord GmbH und Co KG	Rostock	Mecklenburg-Vorpommern
Germany	Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, I. Chirurgische Klinik	Rotenburg (Wümme)	Niedersachsen
Germany	Leopoldina-Krankenhaus, Medizinische Klinik II	Schweinfurt	Bayern
Germany	Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz	Singen	Baden-Württemberg
Germany	Praxisgemeinschaft Dr. Hancken und Partner, Onkologische Schwerpunktpraxis	Stade	Niedersachsen
Germany	Klinikum Mutterhaus der Borromäerinnen gGmbH, Innere Medizin I	Trier	Rheinland-Pfalz
Germany	Kreiskliniken Traunstein -Trostberg GmbH , Innere Medizin/ Hämatologie und Onkologie	Trostberg	Bayern
Germany	Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I	Ulm	Baden-Württemberg
Germany	Sophien- und Hufeland-Klinikum gGmbH, Klinik für Innere Medizin II	Weimar	Thüringen
Germany	Lahn-Dill-Kliniken GmbH, Darmzentrum	Wetzlar	Hessen
Germany	Internistische Gemeinschaftspraxis	Witten	Nordrhein-Westfalen
Germany	HELIOS Klinikum Wuppertal , Medizinische Klinik I	Wuppertal	Nordrhein-Westfalen

Sponsors (1)

Lead Sponsor	Collaborator
AIO-Studien-gGmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo		6 to 12 months	No
Secondary	Disease control rate		6 to 12 months	No
Secondary	Overall survival		6 to 12 months	No
Secondary	Response rates		6 to 12 months	No
Secondary	Safety		signature of informed consent until 30 days after end of treatment	Yes

External Links

•   Arbeitsgemeinschaft der internistischen Onkologie