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

A Phase I, Multi-center, Non-randomized, Open Label, Parallel-group Study Evaluating the Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment Compared to a Control Group

To characterize the pharmacokinetics and safety of regorafenib in cancer subjects with severe renal impairment when compared to the Control group (cancer subjects with normal or mildly impaired renal function)

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