Patients with advanced renal cell carcinoma
Conditions
Interventions
Product Name: Sorafenib
Product Code: Bay 43-9006
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sorafenib
CAS Number: 284461-73-0
Current Sponsor code: Bay 43-9006
Concentration unit: m
Sponsors
Univ. Prof. Dr. Manuela Schmidinger
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age greater or equal to 18 years • Histologically confirmed renal cell carcinoma (primary tumour or biopsy/surgery of metastases) • Radiologically confirmed metastatic disease • Surgically removed primary tumour so feasible (nephrectomy or nephron-sparing surgery as indicated) • ECOG status of 0 or 1 • Life expectancy of at least 12 weeks • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to treatment start: o Hemoglobin > 9.0 g/L o Leucocytes greater than or equal to 3000/µL o Absolut neutrophil count > or equal 1,500 µL o Platelet count above > or equal 100,000 /µL o Total bilirubin > or equal 1.5 x upper limit normal o Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Prior systemic treatment for advanced renal cell carcinoma • Previous or concurrent malignancy 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 and T1) or any cancer curatively treated > 5 years prior to study entry. • Complete renal shut down requiring hemo-or peritoneal dialysis • History of cardiac disease: congestive heart failure > NYHA class 2, active cardiovascular disease (MI less than 6 months prior to study entry), cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers and digoxins are permitted), uncontrolled hypertension or history of poor compliance with antihypertensive treatment • Active clinically serious bacterial or fungal infection (> grade 2 NCI-CTCAE, Version 3) • Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B/C • Evidence of spinal cord compression or brain metastases. A CT or MRI of the brain must be performed within 4 weeks prior to enrolment if the presence of metastases at these sites is suspected. • History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy e.g. uncontrolled seizures. • Patients with evidence or history of bleeding diathesis, coagulopathy, or thromboembolic event • Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results • Known or suspected allergy to any agent given in association with this trial • Any condition that is unstable or which could jeopardize the safety of the patient and his compliance in the study (e.g. uncontrolled diabetes mellitus, pancreatitis, acute or chronic liver disease etc). • Investigational drug therapy outside this trial during or within 4 weeks of the study entry • Prior use of inhibitors of Ras/Raf-, MEK-, AKT kinase- and mTOR-signaling pathway or of Farnesyl transferase inhibitors • Prior use investigational or licensed angiogenesis inhibitors • Concomitant Rifampicin • Significant surgery within 4 weeks prior to study entry • Female patients who are pregnant or breast feeding • Proteinuria defined as a 24-hour urine protein excretion greater than 1000 mg. Urine dipstick proteinuria of 2+ or greater will require a 24 hour urine to determine eligibility for enrollment • Impairment of the gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Sorafenib • Therapeutic anticoagulation with coumadin, heparins or heparinoids • Current or recent (within 10 days of first dose of study treatment) daily use of aspirin (>325 mg/day) or other NSAID • Thrombic or embolic events within the past 6 months • Hypertension defined as systolic blood pressure greater than 140 mm/Hg or diastolic pressure greater than 90 mm/Hg despite optimal management • Serious non-healing wounds, acute or non-healing ulcers, or bone fractures • Evidence of bleeding diathesis • History of hemoptysis or high grade varices • Primary tumor surgically removable • Solitary, surgically removable metastases • Patient unwilling or unable to give informed consent • Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the combination of Sorafenib and Bevacizumab with respect to progression free survival ;Secondary Objective: • To assess the safety of Sorafenib and Bavacizumab when used in combination • To assess disease control rate (DCR) • To estimate response rate • To evaluate time to progression (TTP) • To evaluate overall survival (OS) • To evaluate Quality of Life • To compare VEGF plasma levels before and during the treatment ;Primary end point(s): Clinical response measured according to standard criteria • Progression free survival • clinical adverse events • laboratory parameters | — |
Countries
Austria
Outcome results
None listed