Sorafenib Dose Escalation in Renal Cell Carcinoma

A Phase II, Multi-centre, Open-label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Intrapatient Dose Escalation of Sorafenib as First Line Treatment for Metastatic Renal Cell Carcinoma.

Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib works by stopping the development of new cancer cells and new blood vessels. By stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth of kidney cancer tumors.

This is an "open-label" study which means that the patient, the doctor and Bayer Healthcare will know what tablets the patient is taking. All patients in this study will receive sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day). Treatment with sorafenib will continue until the patient's tumor grows larger or spreads further or if the patient has intolerable side effects. The dose of sorafenib that the patient will receive in the study will increase at certain points during the patient's treatment, as long as the patient is not experiencing side effects and the patient's tumor has not grown.

Issues on Outcome Measure "Safety and tolerability" will be addressed in the Adverse Events section.

Inclusion Criteria:

• Age > 18 years.
• Metastatic clear cell RCC (renal cell carcinoma)
• Subjects with at least one uni-dimensional measurable lesion.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category
• 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 7 days prior to treatment
• Signed informed consent must be obtained prior to any study specific procedures.
• Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma
• Prior total nephrectomy

Exclusion Criteria:

• History of cardiac disease
• History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 3.0)
• Symptomatic metastatic brain or meningeal tumors unless the subject 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.
• Subjects with evidence or history of bleeding diathesis
• Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment.
• Delayed healing of wounds, ulcers or bone fractures
• Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication
• Subjects undergoing renal dialysis
• Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and three months after the completion of trial.
• Prior adjuvant sorafenib is excluded.
• Radiotherapy during study or within 3 weeks of start of study drug
• Major surgery within 4 weeks of start of study
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry