Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment

Inclusion Criteria

• Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy
• Male or female subject ≥ 18 years of age
• Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before start of study treatment
• Life expectancy at least 8 weeks
• Adequate bone marrow, and liver function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• For subjects with NORMAL OR MILDLY IMPAIRED RENAL FUNCTION (Control group); to be tested within 7 days of starting the study treatment:
• Estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using the Cockcroft-Gault equation
• For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of starting the study treatment:
• CLcr 15-29 mL/min as calculated using the Cockcroft-Gault equation

Exclusion Criteria

• Symptomatic metastatic brain or meningeal tumors
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• History of organ allograft
• Non-healing wound, skin ulcer, or bone fracture
• Pheochromocytoma
• Uncontrolled concurrent medical illness including uncontrolled hypertension
• History of cardiac disease
• Pleural effusion or ascites that causes respiratory compromise
• Interstitial lung disease with ongoing signs and symptoms at the time of screening
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication
• Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event NCI-CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment
• Dehydration NCI-CTCAEversion 4.0 Grade ≥ 1
• Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 attributed to any prior therapy/procedure (excluding alopecia or anemia or grade 2 neuropathy that is not reversible due to oxaliplatin)
• Seizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics)
• For subjects with SEVERELY IMPAIRED renal function:
• Renal failure requiring hemo- or peritoneal dialysis
• Acute renal failure
• Acute nephritis
• Nephrotic syndrome