BAY43-9006 (Sorafenib) Versus Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma

A Randomised, Open-label, Multi-centre Phase II Study of BAY43-9006 (Sorafenib) Versus Standard Treatment With Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma.

The purpose of the study is to:

• Find out if patients receiving BAY43-9006 will live longer without tumor progression than those receiving standard therapy with interferon alpha-2a
• Find out if a higher dose of BAY43-9006 can inhibit tumor progression in patients who progressed during standard dose treatment with BAY43-9006, and for how long these patients live without progression
• Find out how long patients live without progression who receive BAY43-9006 after failing to respond to standard therapy with interferon alpha-2a
• Find out in how many percent of patients BAY43-9006 prevents the growth of or shrinks kidney tumors and/or their metastases depending on treatment and dosage
• Find out if BAY43-9006 has any effect on the quality of life of patients with kidney cancer
• Find out the level of BAY43-9006 in the blood once per month and any changes in this level
• Find out whether BAY43-9006 effects are associated with specific biomarkers

Analyses on Biomarkers were exploratory and assessed as tertiary objective of the trial.

Inclusion Criteria:

• Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
• Male or female patients >= 18 years of age
• Patients who have a life expectancy of at least 12 weeks
• Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (Renal Cell Carcinoma) histologically or cytologically documented
• Patients must have undergone prior (at the time of primary diagnosis) complete surgical excision of primary RCC tumor
• Patients must have had no prior systemic therapy for advanced RCC. Prior systemic therapy is defined as any treatment with a chemotherapy agent (or regimen), an immunotherapy agent (or regimen) or an investigational treatment agent (or regimen) against the renal cell carcinoma. Megestrol acetate or medroxyprogesterone will constitute as a prior systemic therapy
• Patients who have at least one uni-dimensional measurable lesion by CT (Computed tomography)-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
• 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/l
• Absolute neutrophil count ( ANC)>1,500/mm3
• Platelets> or = 100,000/ul
• Total bilirubin < 1.5 x the upper limit of normal
• ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
• Amylase and lipase < 1.5 x the upper limit of normal
• Serum creatinine < 2.0 x the upper limit of normal
• PT (Prothrombin Time) or INR (International Normalized Ratio) and PTT (Partial Thromboplastin Time) < 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)

Exclusion Criteria:

• 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 [Noninvasive papillary carcinoma], Tis [Carcinoma in situ: "flat tumor"]&T1 [Tumor invades subepithelial connective tissue]) 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 (New York Heart Association) class 2: active cardiovascular disease( MI (Distant metastasis) more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
• Active clinically serious bacterial or fungal infections (>= grade 2 NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), Version 3)
• Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• 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 this brain tumour site at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies (head CT or MRI at screening always required)
• Patients with seizure disorder requiring medication (such as steroid anti-epileptics)
• History of organ allograft
• 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 the investigational agent or any agent given in association with this trial
• Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of 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