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

Phase 2

Terminated

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

• Registration Number: NCT00889343
• Lead Sponsor: AIO-Studien-gGmbH

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.

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2009-04-17
• Study First Submitted QC: 2009-04-27
• Study First Posted: 2009-04-28
• Primary Completion: 2011-11
• Study Completion: 2012-12
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-01
• Last Update Posted: 2013-03-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 101

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Oxaliplatin or Irinotecan	-
2	Placebo	-
2	Oxaliplatin or Irinotecan	-
1	Leucovorin	-
2	Leucovorin	-
1	Sorafenib	-
1	5-Fluorouracil	-
2	5-Fluorouracil	-

Primary Outcome Measures

Name	Time	Method
To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo	6 to 12 months

Secondary Outcome Measures

Name	Time	Method
Safety	signature of informed consent until 30 days after end of treatment
Disease control rate	6 to 12 months
Overall survival	6 to 12 months
Response rates	6 to 12 months

Trial Locations

Locations (56)

Medizinisches Versorgungszentrum am Siloah St. Trudpert Klinikum; 🇩🇪 Pforzheim, Baden-Würtemberg, Germany

Ostalb-Klinikum Aalen, Medizinische Klinik 1; 🇩🇪 Aalen, Baden-Württemberg, Germany

Kreiskliniken Esslingen gGmbH, Klinik Nürtingen, Medizinische Klinik I; 🇩🇪 Nürtingen, Baden-Württemberg, Germany

Gemeinschaftspraxis Onkologie Ravensburg; 🇩🇪 Ravensburg, Baden-Württemberg, Germany

Gemeinschaftspraxis Dr. med. U. Banhardt, Dr. med. T. Fietz; 🇩🇪 Singen, Baden-Württemberg, Germany

Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I; 🇩🇪 Ulm, Baden-Württemberg, Germany

Überörtliche Gemeinschaftspraxis Dres. Wilke und Wagner; 🇩🇪 Fürth, Bayern, Germany

Hämatologischonkologische Schwerpunktpraxis; 🇩🇪 Herrsching, Bayern, Germany

Hämatologie Onkologie Tagesklinik Landshut; 🇩🇪 Landshut, Bayern, Germany

Hämato-Onkologische Schwerpunktpraxis Prof. Salat / Dr. Stoetzer / Prof. Hiller; 🇩🇪 München, Bayern, Germany

Scroll for more (46 remaining)