A clinical study of a new drug called E7080 for patients with cancer of the womb that has spread to other parts of the body after having one platinum based chemotherapy. The patients know they are receiving the drug. The study is being done in different countries and the safety and effectivenes of E7080 have already been studied in other cancer patients.
- Conditions
- nresectable endometrial cancer and disease progression following platinum-based, first-line chemotherapyMedDRA 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)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-016858-41-HU
- Lead Sponsor
- Eisai Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- Female
- Target Recruitment
- 130
1) Histologically confirmed diagnosis of endometrial carcinoma.
2)Radiographic evidence of disease progression according to RECIST 1.1(Appendix 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 disease 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 (revised per Amendment 02).
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 computerized tomography/magnetic resonance imaging (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 (revised per Amendment 02).
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of
progressive disease based on RECIST 1.1 to be deemed a target lesion.
4) Eastern Cooperative Oncology Group (ECOG) performance status =2 (Appendix 2).
5) Adequately controlled blood pressure (BP) 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 (revised per Amendment 01).
6) Adequate renal function defined as calculated creatinine clearance =30 mL/min per the Cockcroft and Gault formula (Appendix 3) (revised per Amendment 01).
7) Adequate bone marrow function:
- Absolute neutrophil count (ANC) =1000/mm3 (=1.0 x 103/µ/L);
- Platelets =100,000/mm3 (=100 x 109/L);)
- Hemoglobin =9.0 g/dL
8) Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) =1.5.
9) Adequate liver function:
- Bilirubin =1.5 x the upper limit of normal (ULN) except for unconjugated hyperbilirubinaemia of Gilbert’s syndrome;
- Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x ULN (=5 x ULN if subject has liver metastases).
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-human chorionic gonadotropin [ß-hCG] test with a
minimum sensitivity of 25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. (revised per Amendment 02)
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) (revised per Amendment 02).
13) Females of childbearing potential must not have had unprotected sexual
1) Brain or leptomeningeal metastases, including stable metastases (added per Amendment 01).
2) More than 1 prior systemic chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma or any treatment targeting vascular endothelial
growth factor (VEGF)-directed angiogenesis. There is no restriction regarding prior hormonal therapy (revised per Amendment 02).
3) Prior systemic anti-tumor therapy within 3 weeks.
4) Not fully recovered from prior radiotherapy based on investigator judgment(added per Amendment 01).
5) Subjects with >1+ proteinuria on urine dipstick will undergo 24-hour urine collection for quantitative assessment of proteinuria (revised per Amendments 01 and 02). 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 cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 4); 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] is allowed).
12) Active hemoptysis (bright red blood of at least ½ 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 or 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 squamous cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix) in the past
2 years (revised per Amendments 01 and 02).
16) Previous treatment with an investigational drug within 30 days prior to the first dose of study drug.
17) Females who are pregnant or breastfeeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the objective response rate (ORR: complete response + partial response [CR+ PR]) of E7080 in subjects with unresectable endometrial cancer and disease progression following platinum-based, first-line chemotherapy.;Secondary Objective: To assess progression-free survival (PFS) and overall survival (OS) of subjects in this study population when treated with E7080.To assess the disease control rate (DCR: CR + PR + stable disease [SD =7 weeks]);<br>clinical benefit rate (CBR: CR + PR + durable SD [SD =23 weeks]); and durable SD rate.To assess the safety and tolerability of E7080. To assess the pharmacokinetic (PK) profile and pharmacodynamics of E7080 in subjects with advanced endometrial cancer.<br>;Primary end point(s): Objective tumour response rate (CR + PR) based on modified RECIST 1.1 ;Timepoint(s) of evaluation of this end point: Disease control rate (CR + PR + SD) based on RECIST 1.1 and minimum duration<br>of SD lasting =7 weeks.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival based on RECIST 1.1 and measured as the time from the<br>date of first treatment until the date of first documentation of disease progression or<br>date of death, if death occurs prior to disease progression.;Timepoint(s) of evaluation of this end point: Clinical benefit rate (CR + PR + durable SD) based on RECIST 1.1 and SD lasting<br>=23 weeks.<br>Durable SD rate based on RECIST 1.1 and defined as SD lasting =23 weeks.