Effects of LBM and PPIs on Pharmacokinetics and Safety of Regorafenib (BAY 73-4506) in Cancer Patients

Exclusion Criteria

• •Prior treatment with regorafenib. Patients permanently withdrawn from the study will not be allowed to re-enter the study
• •Symptomatic metastatic brain or meningeal tumors unless the patient is greater than 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within four weeks prior to study entry and is not on dexamethasone and clinically stable with respect to the tumor at the time of surgery.
• •Major surgery, open biopsy or significant traumatic injury within 28 days before starting the study treatment.
• •History of organ allograft.
• •Non-healing wound, skin ulcer or bone fracture.
• •Uncontrolled intercurrent medical illness including uncontrolled hypertension defined as systolic blood pressure \> 150 millimeters of mercury (mmHg) or diastolic blood pressure \> 90 mmHg, despite medical management
• •History of cardiac disease: congestive heart failure \> New York Heart Association (NYHA) Class II; unstable angina (symptoms of angina at rest), new-onset angina (within the last 3 months), myocardial infarction within the past 6 months prior to screening (Visit 1); cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (expect for beta-blockers and digoxin).
• •Pleural effusion or ascites with causes respiratory compromise (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Grade ≥ 2 dyspnea).
• •Interstitial lung disease with ongoing signs and symptoms within 28 days before starting the study treatment
• •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 CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment.
• •Dehydration CTCAE Grade ≥1
• •Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 (excluding alopecia, anemia or lymphopenia) attributed to any prior systemic or radiation therapy or other medical or surgical procedure
• •Known hypersensitivity to regorafenib, study drug class, or excipients in the formulation.
• •Ongoing or active infection (bacterial, fungal or viral, e.g. human immunodeficiency virus (HIV)) of NCI-CTCAE version 4.0 Grade ≥ 2
• •Seizure disorder requiring anti-convulsant therapy (such as steroids or anti-epileptics)
• •Pregnancy and lactation (breastfeeding)
• •During the study, no other anticancer treatment, including any investigational new drugs, is allowed. Anticancer therapy is defined as any agent or combination of agents with clinically proven anticancer activity. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy during this trial or within 28 days or 5 drug half lives (if drug half-life in subject is known), whichever is shorter (or within 6 weeks or mitomycin C) before start of the study treatment
• •Use of hematopoietic growth factors, such as G-CSF (granulocyte colony-stimulating factor), GM-CSF (granulocyte-macrophage colony-stimulating factor), erythropoietin, and interleukin (IL-2, IL-3), within 3 weeks prior to first dose. Subjects taking chronic erythropoietin consistent with institutional guidelines can be included.
• •Close affiliation with the investigational site; e.g. a close relative of the investigator or a dependent person (e.g. employee or student of the investigational site)
• •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• •Inability to swallow oral medications.