Study of E7080 in Subjects With Advanced Endometrial Cancer and Disease Progression

Inclusion criteria:

Histologically confirmed diagnosis of endometrial carcinoma Radiographic evidence of disease progression according to modified RECIST 1.1 after 1 prior systemic, platinum-based chemotherapy regimen for recurrent metastatic or primary unresectable endometrial carcinoma for which no surgical or radiotherapy treatment option exists

Measureable disease meeting the following criteria:

• At least 1 lesion of >1.5 cm in the longest diameter for a non-lymph node or >1.5 cm in the short-axis diameter for a lymph node which is is serially measureable according to modified RECIST 1.1 using computerized tomography / magnetic resonance imaging
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency ablation must show evidence of progressive disease based on modified RECIST 1.1 to be deemed a target lesion.

Eastern Cooperative Oncology Group (ECOG) performance status <2. Adequately controlled blood pressure with or without antihypertensive medications, defined as BP <150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit Adequately renal function defined as calculated creatinine clearance >30 mL/min per the Cockcroft and Gault formula

Adequate bone marrow function:

• Absolute neutrophil count >1000/mm3 (>1.0 x 103/u/L);
• Platelets >100,000/mm3 (>100 x 109/L);
• Hemoglobin >9.0 g/dL Adequate blood coagulation function as evidenced by an International Normalized Ratio <1.5

Adequate liver function:

• Bilirubin <1.5 x ULN except for unconjugated hyperbilirubinaemia of Gilbert's syndrome
• Alkaline Phosphatase, alanine aminotransferase and aspartate aminotransferase < 3 X ULN (<5 x ULN if subject has liver metastasis) Age > 18 years at time of informed consent Must have negative serum or urine pregnancy test for women of reproductive potential

Exclusion criteria:

Brain or leptomeningeal metastases, including stable metastases More than 1 prior systemic chemotherapy regimen for recurrent metastatic or primary unresectable endometrial carcinoma or any treatment targeting vascular endothelial growth factor (VEGF)-directed angiogenesis. No restriction regarding prior adjuvant chemotherapy or hormonal therapy Prior systemic anti-tumor therapy within 3 weeks Not fully recovered from prior radiotherapy based on investigator judgement Subjects with > 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with > 1 gm will be ineligible Gastrointestinal malabsorption or any other condition that might affect teh absorption of E7080 Inability to take oral medication Major surgery within 3 weeks prior to first dose of study drug Significant cardiovascular impairment: hx of congestive heart failure greater than New York Heart Association Class II; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; cardiac arrhythmia requiring medical treatment Prolongation of QTc interval >480 msec. Bleeding disorder or thrombotic disorders requiring anticoagulant therapy, such as warfarin, or similar agents requiring therapeutic INR monitoring (treatment with low molecular weight heparin [LMWH] allowed).

Active hemoptysis within 3 weeks prior to the first dose of study drug Known intolerance to the study drug ( or any of the excipients) Any medical or other conditions which, in the opinion of the investigator, would preclude participation in a clinical trial Active malignancy in the past 2 years other than endometrial cancer unless histologic proof is available demonstrating that recurrent disease is a relapse of endometrial carcinoma Previous treatment with an investigational drug within 30 days prior to first dose of study drug Females who are pregnant or breast feeding.