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

NCT00889343 | Terminated Phase 2 DMC

• 1 other identifier: AIO KRK 0307
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 57

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.

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

Outcome Measures

Primary Outcomes (1)

• To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo

  6 to 12 months

Secondary Outcomes (4)

• Disease control rate

  6 to 12 months

• Overall survival

  6 to 12 months

• Response rates

  6 to 12 months

• Safety

  signature of informed consent until 30 days after end of treatment

Study Arms (2)

1

EXPERIMENTAL

Drug: Sorafenib; Drug: Oxaliplatin or Irinotecan; Drug: Leucovorin; Drug: 5-Fluorouracil

2

PLACEBO COMPARATOR

Drug: Placebo; Drug: Oxaliplatin or Irinotecan; Drug: Leucovorin; Drug: 5-Fluorouracil

Interventions

Sorafenib DRUG

2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral

Also known as: Nexavar

1

Placebo DRUG

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

2

Oxaliplatin or Irinotecan DRUG

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

1; 2

Leucovorin DRUG

400 mg/m2 intravenous infusion on day 1 of a 14-days cycle

1; 2

5-Fluorouracil DRUG

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

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead

Study Sites (57)

Ostalb-Klinikum Aalen, Medizinische Klinik 1

Aalen, Baden-Wurttemberg, 73428, Germany

Location

Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Gemeinschaftspraxis Onkologie Ravensburg

Ravensburg, Baden-Wurttemberg, 88214, Germany

Location

Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz

Singen, Baden-Wurttemberg, 78224, Germany

Location

Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I

Ulm, Baden-Wurttemberg, 89070, Germany

Location

Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum

Pforzheim, Baden-Würtemberg, 75179, Germany

Location

Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner

Fürth, Bavaria, 90766, Germany

Location

Hämatologischonkologische Schwerpunktpraxis

Herrsching am Ammersee, Bavaria, 82211, Germany

Location

Hämatologie Onkologie Tagesklinik Landshut

Landshut, Bavaria, 84028, Germany

Location

Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller

München, Bavaria, 80639, Germany

Location

Leopoldina-Krankenhaus, Medizinische Klinik II

Schweinfurt, Bavaria, 97422, Germany

Location

Kreiskliniken Traunstein -Trostberg GmbH , Innere Medizin/ Hämatologie und Onkologie

Trostberg an der Alz, Bavaria, 83308, Germany

Location

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II

Bremen, City state Bremen, 28239, Germany

Location

MVZ für Innere Medizin in Hamburg Eppendorf

Hamburg, Hamburg, 20248, Germany

Location

Klinikum Darmstadt, Medizinische Klinik V

Darmstadt, Hesse, 64283, Germany

Location

Städtische Kliniken Frankfurt a.M. - Höchst, Klinik für Innere Medizin Abt. 3

Frankfurt a.M., Hesse, 65929, Germany

Location

Vitanus GmbH

Frankfurt am Main, Hesse, 60596, Germany

Location

Klinikum Fulda, Tumorklinik

Fulda, Hesse, 36043, Germany

Location

Onkologische Praxisgemeinschaft Dres. Siehl, Söling und Prof. Hirschmann

Kassel, Hesse, 34117, Germany

Location

Philipps-Universität, Klinikum Marburg, Klinik für Innere Medizin mit SP Hämatologie und Onkologie

Marburg, Hesse, 35043, Germany

Location

Gemeinschaftspraxis für Hämatologie und Internistische Onkologie

Offenbach, Hesse, 63065, Germany

Location

Lahn-Dill-Kliniken GmbH, Darmzentrum

Wetzlar, Hesse, 35578, Germany

Location

MediProjekt, Gesellschaft für Medizinstatistik und Projektentwicklung

Hanover, Lower Saxony, 30171, Germany

Location

Krankenhaus Siloah, Medizinische Klinik III

Hanover, Lower Saxony, 30449, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie

Hanover, Lower Saxony, 30625, Germany

Location

Onkologische Schwerpunktpraxis Hildesheim

Hildesheim, Lower Saxony, 31135, Germany

Location

Hämatologie u. Internistische Onkologie

Lehrte, Lower Saxony, 31275, Germany

Location

Hämatologisch-onkologische Schwerpunktpraxis Northeim

Northeim, Lower Saxony, 37154, Germany

Location

Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH,

Osnabrück, Lower Saxony, 49074, Germany

Location

Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, I. Chirurgische Klinik

Rotenburg (Wümme), Lower Saxony, 27356, Germany

Location

Praxisgemeinschaft Dr. Hancken und Partner, Onkologische Schwerpunktpraxis

Stade, Lower Saxony, 21680, Germany

Location

Universitätsklinikum Rostock, Klinik für Innere Medizin

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Wissenschaftskontor Nord GmbH und Co KG

Rostock, Mecklenburg-Vorpommern, 18107, Germany

Location

Medizinische Universitätsklinik-Knappschaftskrankenhaus, Medizinische Klinik

Bochum, North Rhine-Westphalia, 44892, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie am Sachsenring

Cologne, North Rhine-Westphalia, 50677, Germany

Location

St. Vincenz-Krankenhaus, Medizinische Klinik I

Datteln, North Rhine-Westphalia, 45711, Germany

Location

St. Antonius Hospital, Klinik für Hämatologie / Onkologie

Eschweiler, North Rhine-Westphalia, 52249, Germany

Location

Hämato-Onkologisches Gemeinschaftspraxis

Essen, North Rhine-Westphalia, 45136, Germany

Location

Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und Onkologie

Hagen, North Rhine-Westphalia, 58095, Germany

Location

Klinikum Leverkusen gGmbH, Medizinische Klinik III

Leverkusen, North Rhine-Westphalia, 51375, Germany

Location

Gemeinschaftspraxis Hämatologie und Onkologie

Münster, North Rhine-Westphalia, 48149, Germany

Location

Praxis und Tagesklinik für Internistische Onkologie und Hämatologie

Recklinghausen, North Rhine-Westphalia, 45657, Germany

Location

Prosperhospital Recklinghausen, Medizinische Klinik I

Recklinghausen, North Rhine-Westphalia, 45659, Germany

Location

Internistische Gemeinschaftspraxis

Witten, North Rhine-Westphalia, 58452, Germany

Location

HELIOS Klinikum Wuppertal , Medizinische Klinik I

Wuppertal, North Rhine-Westphalia, 42283, Germany

Location

I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Klinikum Mutterhaus der Borromäerinnen gGmbH, Innere Medizin I

Trier, Rhineland-Palatinate, 54290, Germany

Location

Universitätskliniken des Saarlandes, Innere Medizin I

Homburg / Saar, Saarland, 66421, Germany

Location

Hämatologisch-onkologische Praxis Dr. med. Peter Schmidt

Neunkirchen, Saarland, 66821, Germany

Location

Praxisgemeinschaft Dr. med. Thomas Göhler und Steffen Dörfel

Dresden, Saxony, 01127, Germany

Location

Internistische Praxis & Tagesklinik

Neutstadt/Sachsen, Saxony, 01844, Germany

Location

Städtisches Klinikum Dessau, Klinik für Innere Medizin

Dessau, Saxony-Anhalt, 06847, Germany

Location

Onkologische Gemeinschaftspraxis

Halle, Saxony-Anhalt, 06110, Germany

Location

Gemeinschaftspraxis für Hämatologie und Internistische Onkologie

Magdeburg, Saxony-Anhalt, 39104, Germany

Location

Friedrich-Ebert-Krankenhaus Neumünster, Klinik für Hämatologie, Onkologie und Nephrologie

Neumünster, Schleswig-Holstein, 24534, Germany

Location

eps-early phase solution GmbH

Jena, Thuringia, 07743, Germany

Location

Sophien- und Hufeland-Klinikum gGmbH, Klinik für Innere Medizin II

Weimar, Thuringia, 99425, Germany

Location

Related Links

• Arbeitsgemeinschaft der internistischen Onkologie

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Sorafenib; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines

Study Officials

• Thomas Höhler, Prof. Dr. med.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2009
• First Posted: April 28, 2009
• Study Start: March 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: December 1, 2012
• Last Updated: March 4, 2013

Record last verified: 2013-03

Locations

DE (57)