An Open-Label, Single-Arm, Multicenter Phase 2 Study of E7080 in Subjects with Advanced Endometrial Cancer and Disease Progression Following First-Line Chemotherapy

Conditions: nresectable endometrial cancer and disease progression following platinum-based, first-line chemotherapy
MedDRA version: 14.0Level: PTClassification code 10014740Term: Endometrial cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0Level: PTClassification code 10014736Term: Endometrial cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0Level: PTClassification code 10014734Term: Endometrial cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0Level: PTClassification code 10014741Term: Endometrial cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2009-016858-41-BG

Lead Sponsor: Eisai Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 130

Inclusion Criteria

1) Histologically confirmed diagnosis of endometrial carcinoma.
2) Radiographic evidence of disease progression according to RECIST 1.1 after 1 prior systemic, platinum-based chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma for which no surgical or radiotherapy treatment options exist. Patients with desease progression within 1 year following completion of platinum-based chemotherapy administered as either adjuvant or neoadjuvant treatment will be eligible without the requirement for further systemic treatment. Patients who have received platinum-based adjuvant or neoadjuvant treatment and have disease progression more than 1 year following treatment must receive 1 additional cytotoxic systemic treatment before being eligible for enrollment in this study.
3) Measurable disease meeting the following criteria:
-At least 1 lesion of >/=1.0 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 serially measurable according to RECIST 1.1 using CT/MRI. If there is only 1 target lesion, and it is a non-lymph node, it should have a longest diameter of >/=1.5 cm.
-Lesions that have had EBRT or loco-regional therapies such as RF ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
4) ECOG performance status 5) Adequately controlled BP with or without antihypertensive mediciations, defined as BP 6) Adequate renal function defined as calculated creatinine clearance >/=30 mL/min per the Cockcroft and Gault formula
7) Adequate bone marrow function:
-ANC >/=1000/mm3
-Platelets >/=100,000/mm3
-Hemoglobin >/=9.0 g/dL
8) Adequate blood coagulation function as evidenced by an INR 9) Adequate liver function:
-Bilirubin -ALT and AST 10) Females age >/=18 years at the time of informed consent
11) Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-hCG test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment if required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
12) All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
13) Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug disconti

Exclusion Criteria

1) Brain or leptomeningeal metastases including stable metastases
2) More than 1 prior systemic chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma or any teatment targetting VEGF-directed angiogenesis. There is no restriction regarding prior hormonal therapy
3) Prior systemic anti-tumour therapy within 3 weeks
4) Not fully recovered from prior radiotherapy based on investigator judgment
5) Subjects with >1+ proteinuria on urine dipstick will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with 24-hour urine protein >/=1 g will be ineligible
6) Gastrointestinal malabsorption or any other condition that might affect the absorption of E7080
7) Inability to take oral medication
8) Major surgery within 3 weeks prior to the first dose of study drug
9) Significant cardiobascular impairment: history of congestive heart failure greater than NYHA Class II; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment
10) Prolongation of QTc interval to >480 msec
11) Bleeding disorder or thrombotic disorder requiring anticoagulant therapy, such as warfarin, or similar agents requiring therapeutic INR monitoring (treatment with low molecular weight heparin [LMWH] allowed)
12) Active hemoptysis (bright red blood of at least 1/2 teaspoon) within 3 weeks prior to the first dose of study drug
13) Known intolerance to the study drug (or any of the excipients)
14) Any medical of other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
15) Any malignancy (except for endometrial cancer, basal or aquamos cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix) in the past 2 years
16) Previous treatement with an investigational drug withing 30 days prior to the first dose of study drug
17) Females who are pregnant or breastfeeding