An Open-Label, Single-Arm, Multicenter Phase II Study of E7080 in Subjects With Advanced Endometrial Cancer and Disease Progression Following First-Line Chemotherapy

Inclusion Criteria

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.