An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors

Inclusion criteria

• Patients who have histologically and/or cytologically confirmed solid tumors requiring treatment.
• Patients with solid tumors which are resistant to approved conventional anti-tumor therapies, or for which no appropriate treatment is available.
• Patients who had completed all previous treatments (including surgery and radiotherapy) and supportive care (such as transfusion of blood, blood components and granulocyte colony-stimulating factor [G-CSF] treatment) at least 4 weeks before registration, and no sign or symptom of acute toxicity occurred in previous treatments.
• Patients 20 years or older and less than 75 years of age at the time of registration.
• Patients with 0 or 1 Performance Status (PS) established by Eastern Cooperative Oncology Group (ECOG.)
• Patients who can stay in hospital for more than 1 cycle of treatment.
• Patients who are expected to survive for more than 3 months from the start of study drug administration.
• Patients who have provided written informed consent for the participation in the study.

Exclusion criteria

• Patients with clinical symptoms due to brain metastases requiring treatment.
• Patients who have any of the following laboratory test findings:

• Hemoglobin less than 9.0 g/dL
• Neutrophil count less than 1.5 x 10 9/L
• Platelet count less than 100 x 10 9/L
• Serum bilirubin greater than 1.5 mg/dL
• AST, ALT greater than 100 IU/L
• Serum creatinine greater than 1.5 mg/dL or creatinine clearance less than 50 mL/minute
• Patients with positive reaction for human immunodeficiency virus (HIV) or hepatitis virus C (HCV) antibody or hepatitis B virus surface (HBs) antigen, or patients with untreated serious infections.
• Patients with clinically significant cardiac disorders or unstable ischemic heart diseases including myocardial infarction within six months before the registration for the study.
• Patients with marked Baseline prolongation of QT/QTc interval (QTc interval greater than 450 msec for males or greater than 470 msec for females) using the Fridericia method for QTc analysis.
• Patients with hemorrhagic or thrombotic diseases or who are using therapeutic doses of anticoagulants such as aspirin, warfarin, or ticlopidine.
• Patients who are diagnosed with hypertension (defined as repeatedly measured blood pressure = 160/90 mmHg) at Screening, irrespective of use of antihypertensive drugs.
• Patients who have proteinuria greater than 1 on bedside testing.
• Patients who have history of insufficient gastrointestinal absorption, or patients who received gastric or intestinal anastomoses within 4 weeks before registration.
• Patients who have history of alcoholism, drug addiction or mental or physical disorders, which, in the investigators opinion, may impair study compliance.
• Patients who received any investigational drug within 30 days before the registration of the study.
• Patients who received CYP3A4 inhibitors including itraconazole, erythromycin, clarithromycin, diltiazem or verapamil during screening and who have to use these drugs during the study.
• Pregnant or nursing patients (all female patients with pregnancy potential must have negative pregnancy test performed before registration, and post-menopausal women must be amenorrheic for at least 12 months.) Female patients must use appropriate contraception.
• Fertile male patients who refuse to use contraception, or whose female partners are not using appropriate contraception.
• Patients who are judged by the investigator to be inappropriate for the study.