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. MedDRA version: 14.1 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sorafenib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form
Sponsors
AIO Studien gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age > 18 years 2. ECOG Performance Status of 0 to 2 3. Life expectancy of at least 12 weeks 4. 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. 5. 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 ³ 100,000/µl · Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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 2. History of HIV infection or chronic hepatitis B or C 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 4. 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) 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 6. History of organ allograft 7. Patients with evidence or history of bleeding diathesis 8. Patients undergoing renal dialysis 9. Known deficit in Dihydropyrimidine Deshydrogenase (DPD) 10. Contraindications for the use of atropine in patients receiving FOLFIRI 11. 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. 12. Peripheral sensory neuropathy > CTC grade 2 13. Chronic inflammatory bowel disease; ileus; genetic fructose intolerance 14. Pregnant or breast-feeding patients. 15. 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. 16. Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results 17. 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. Excluded therapies and medications, previous and concomitant: 1. 1. Any other anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry 2. 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 3. Autologous bone marrow transplant or stem cell rescue within 4 months prior to study treatment 4. 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] 5. Investigational drug therapy outside of this trial during or within 4 weeks of study entry 6. Prior exposure to the study drug. 7. Any St. John´s wort containing remedy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo;Secondary Objective: Disease control rate Response rates Overall survival Growth modulation index (change of TTP2/TTP1 ratio) Safety;Primary end point(s): The primary efficacy variable is progression-free survival (PFS) and will be analyzed after at least 186 events (i.e. disease progressions) have occurred. | — |
Countries
Germany
Outcome results
None listed