Open Label Regorafenib Study to Evaluate Cardiovascular Safety Parameters, Tolerability, and Anti-tumor Activity

An Open-label, Non-randomized Phase I Study of Regorafenib (BAY73-4506) to Evaluate Cardiovascular Safety Parameters, Tolerability, Pharmacokinetics, and Anti-tumor Activity in Patients With Advanced Solid Tumors

Open label Phase I study of Regorafenib to evaluate cardiovascular safety, tolerability and anti-tumor activity in patients with advanced solid tumors

Inclusion Criteria:

• Male or female subjects >/= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1

• Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to dosing:

  • Hemoglobin (Hb) >/= 9.0 g/dL, Absolute neutrophil count (ANC) >/= 1500/mm³, Platelet >/= 100,000/mm³, Total bilirubin </= 1.5 times upper limit of normal (ULN), Alkaline phosphatase </= 4 x ULN
  • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) </= 2.5 times ULN (</= 5.0 x ULN for subjects with liver involvement of their cancer), International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) < 1.5 x ULN, Serum creatinine </= 1.5 times ULN and glomerular filtration rate (GFR) >/= 30 ml/min/1.73 m² according to the MDRD (Modified Diet in Renal Disease) abbreviated formula, Lipase </= 1.5 x ULN
  • Left Ventricular Ejection Fraction (LVEF) >/= 50 % as assessed at the Baseline Multigated Acquisition (MUGA) scan
  • QTc (Q-T corrected) </= 470 msec at Screening

• Having advanced, refractory disease

• Life expectancy of at least 3 months

• Recovery from any previous drug/procedure-related toxicity to Common Toxicological Criteria (CTC) Grade 0 or 1 levels (except alopecia), or to baseline preceding the prior treatment.

Exclusion Criteria:

• History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina [anginal symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months).
• Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of >/= 3 antihypertensive drugs or systolic blood pressure greater than 150 mmHg)
• History of or known human immunodeficiency virus (HIV) infection or active hepatitis B or C.
• Subjects with serious non-healing wound, ulcer, or bone fracture
• Subjects with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication
• Persistent proteinuria of CTC Grade 3 or higher (> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample)
• Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry, and is clinically stable with respect to the tumor at the time of study entry
• Clinically significant bleeding (CTC AE Grade 3 or higher) within 30 days before start of study medication.
• Subjects with seizure disorder requiring anticonvulsant medication
• History of organ allograft