Back to resultsStudy of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression
Primary Purpose
Endometrial Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lenvatinib
Sponsored by
About this trial
This is an interventional treatment trial for Endometrial Cancer focused on measuring Advanced Endometrial Cancer
Eligibility 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 greater than 1.0 cm in the longest diameter for a non-lymph node or greater than 1.5 cm in the short-axis diameter for a lymph node which 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 less than 2.
- Adequate controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
- Adequate renal function defined as calculated creatinine clearance greater than 30 mL/min per the Cockcroft and Gault formula.
- Adequate bone marrow, blood coagulation, and liver functions, as defined in the study protocol.
- 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.
- Participants with greater than 1+ proteinuria on urine dipstick testing to undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with greater than 1 gm will be ineligible.
- Significant cardiovascular impairment: history 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 greater than 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.
- Females who are pregnant or breast feeding.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenvatinib 24 mg
Arm Description
Participants with advanced endometrial cancer and disease progression following platinum-based, first line chemotherapy.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was ≤10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR
Secondary Outcome Measures
Progression Free Survival (PFS)
PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death (whichever occurred first), as determined by independent radiologic review (IRR) and Investigator based on RECIST 1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Overall Survival (OS)
OS was the length time in months from the date of first treatment until the date of death from any cause. If death was not observed, OS was censored at the last known alive date or data cut-off. Additional survival follow-up data was collected for all participants who had not withdrawn consent and were alive at the time of the initial survival follow-up as of 26 Nov 2012 data cut-off. Participants who were lost to follow-up at the time of the initial assessment may have been contacted again at the investigator's discretion. Updated survival (based on 26 Nov 2012 cut-off) was derived for these participants if the contact was made successfully.
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with BOR of CR or PR or stable disease (SD) based on RECIST 1.1 and SD lasting greater than or equal to 7 weeks, as determined by IRR and Investigator.
Clinical Benefit Rate (CBR)
CBR was defined as the percentage of participants with BOR of CR or PR or durable stable disease (dSD) [CR + PR + dSD] based on RECIST 1.1. The dSD rate was defined as the percentage of participants with dSD (based on RECIST 1.1 and defined as SD lasting greater than or equal to 23 weeks), as determined by the IRR and Investigator.
Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib
Safety was assessed by monitoring and recording all AEs and SAEs, regular monitoring of hematology, clinical chemistry, and urine values, regular measurement of vital signs, electrocardiograms (ECGs), and echocardiograms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01111461
Brief Title
Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression
Official Title
An Open-Label, Single-Arm, Multicenter Phase II Study of E7080 (Lenvatinib) in Subjects With Advanced Endometrial Cancer and Disease Progression Following First-Line Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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. .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer
Keywords
Advanced Endometrial Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenvatinib 24 mg
Arm Type
Experimental
Arm Description
Participants with advanced endometrial cancer and disease progression following platinum-based, first line chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
E7080, Lenvima
Intervention Description
Lenvatinib 24 mg administered orally, once daily continuously in 28-day cycles to participants with advanced endometrial cancer and disease progression following first-line chemotherapy. Participants continued to receive study drug until disease progression, development of unacceptable toxicity or withdrawal of consent. 'Treatment interruption and subsequent dose reduction' was allowed for participants who experienced lenvatinib-related toxicity.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was ≤10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR
Time Frame
From the date of first administration of study treatment until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to the end of Cycle 6 (as of 21 May 2012 data cut-off)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death (whichever occurred first), as determined by independent radiologic review (IRR) and Investigator based on RECIST 1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Time Frame
From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression or up to approximately 26 months (as of 21 May 2012 data cut-off)
Title
Overall Survival (OS)
Description
OS was the length time in months from the date of first treatment until the date of death from any cause. If death was not observed, OS was censored at the last known alive date or data cut-off. Additional survival follow-up data was collected for all participants who had not withdrawn consent and were alive at the time of the initial survival follow-up as of 26 Nov 2012 data cut-off. Participants who were lost to follow-up at the time of the initial assessment may have been contacted again at the investigator's discretion. Updated survival (based on 26 Nov 2012 cut-off) was derived for these participants if the contact was made successfully.
Time Frame
From date of first administration of study treatment until the date of death, or up to approximately 32 months (as of 26 Nov 2012 data cut-off)
Title
Disease Control Rate (DCR)
Description
DCR was defined as the percentage of participants with BOR of CR or PR or stable disease (SD) based on RECIST 1.1 and SD lasting greater than or equal to 7 weeks, as determined by IRR and Investigator.
Time Frame
From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, or up to approximately 26 months (as of 21 May 2012 data cut-off)
Title
Clinical Benefit Rate (CBR)
Description
CBR was defined as the percentage of participants with BOR of CR or PR or durable stable disease (dSD) [CR + PR + dSD] based on RECIST 1.1. The dSD rate was defined as the percentage of participants with dSD (based on RECIST 1.1 and defined as SD lasting greater than or equal to 23 weeks), as determined by the IRR and Investigator.
Time Frame
From date of first administration of study treatment until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, or up to approximately 26 months (as of 21 May 2012 data cut-off)
Title
Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib
Description
Safety was assessed by monitoring and recording all AEs and SAEs, regular monitoring of hematology, clinical chemistry, and urine values, regular measurement of vital signs, electrocardiograms (ECGs), and echocardiograms.
Time Frame
From the administration of first dose up to 30 days after the last dose, or up to data cut-off (21 May 2012), or up to approximately 26 months.
Other Pre-specified Outcome Measures:
Title
Summary of Plasma Concentration of Lenvatinib
Description
A total of 6 blood samples for pharmacokinetic (PK) analysis were collected from each participant who received lenvatinib once daily.
Time Frame
Predose and 2 hours postdose on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1
Title
Percentage Change From Baseline for the Imaging Biomarker Parameter of the Area Under the Plasma Concentration Curve Blood Normalized (90) (AUCBN (90)) Median for Total Volume
Description
The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of 2 dynamic contrast-enhanced magnetic resonance imaging/diffusion-weighted magnetic resonance imaging (DCE-MRI/DWI MRI) scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included percentage change in initial area under the gadolinium contrast agent time-concentration curve (first 90 seconds, blood normalized) from baseline.
Time Frame
Cycle 1 Day 5
Title
Percentage Change From Baseline in the Contrast Volume Transfer Coefficient (Ktrans) Median
Description
The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of two DCE-MRI/DWI MRI scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included the percentage change in Ktrans for gadolinium chelate movement from the vasculature into the tissue extracellular space from baseline.
Time Frame
Cycle 1 Day 5
Title
Percentage Change From Baseline in the Apparent Diffusion Coefficient (ADC) Median
Description
The antiangiogenic and direct antitumor effects of lenvatinib were assessed by analyses of two DCE-MRI/DWI MRI scans obtained on evaluable participants at Baseline and Cycle 1 Day 5. The scans were obtained using standardized acquisition across sites. DWI sequences totaling approximately 30 seconds were acquired during the DCE-MRI scans. Centralized analysis metrics for DCE-MRI included the percentage change in ADC for gadolinium chelate movement from the vasculature into the tissue extracellular space from baseline.
Time Frame
Cycle 1 Day 5
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 greater than 1.0 cm in the longest diameter for a non-lymph node or greater than 1.5 cm in the short-axis diameter for a lymph node which 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 less than 2.
Adequate controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
Adequate renal function defined as calculated creatinine clearance greater than 30 mL/min per the Cockcroft and Gault formula.
Adequate bone marrow, blood coagulation, and liver functions, as defined in the study protocol.
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.
Participants with greater than 1+ proteinuria on urine dipstick testing to undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with greater than 1 gm will be ineligible.
Significant cardiovascular impairment: history 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 greater than 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.
Females who are pregnant or breast feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eisai Medical Services
Organizational Affiliation
Eisai Limited
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Scottsdale
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Honolulu
State/Province
Hawaii
Country
United States
City
Arlington Heights
State/Province
Illinois
Country
United States
City
Niles
State/Province
Illinois
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Burnsville
State/Province
Minnesota
Country
United States
City
Edina
State/Province
Minnesota
Country
United States
City
Maplewood
State/Province
Minnesota
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Saint Paul
State/Province
Minnesota
Country
United States
City
Woodbury
State/Province
Minnesota
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Morristown
State/Province
New Jersey
Country
United States
City
New York
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Cleveland
State/Province
North Carolina
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
City
Eugene
State/Province
Oregon
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Springfield
State/Province
Oregon
Country
United States
City
Tualatin
State/Province
Oregon
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Bedford
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Tyler
State/Province
Texas
Country
United States
City
Newport News
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Virginia Beach
State/Province
Virginia
Country
United States
City
Vancouver
State/Province
Washington
Country
United States
City
Arlon
Country
Belgium
City
Charleroi
Country
Belgium
City
Duffel
Country
Belgium
City
Ghent
Country
Belgium
City
Kortrijk
Country
Belgium
City
Leuven
Country
Belgium
City
Liege
Country
Belgium
City
Namur
Country
Belgium
City
Oostende
Country
Belgium
City
Roeselare
Country
Belgium
City
Yvoir
Country
Belgium
City
Pleven
Country
Bulgaria
City
Plovdiv
Country
Bulgaria
City
Sofia
Country
Bulgaria
City
Varna
Country
Bulgaria
City
Veliko Tarnovo
Country
Bulgaria
City
Budapest
Country
Hungary
City
Gyor
Country
Hungary
City
Lublin
Country
Poland
City
Poznan
Country
Poland
City
Warsaw
Country
Poland
City
Brasov County
Country
Romania
City
Bucharest
Country
Romania
City
Cluj County
Country
Romania
City
Dolj County
Country
Romania
City
Kazan
Country
Russian Federation
City
Nizhny Novgorod
Country
Russian Federation
City
Orenburg
Country
Russian Federation
City
Petersburg
Country
Russian Federation
City
Pyatigorsk
Country
Russian Federation
City
Sochi,
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
Stavropol
Country
Russian Federation
City
Syktyvkar
Country
Russian Federation
City
Tomsk
Country
Russian Federation
City
Tula
Country
Russian Federation
City
Ufa
Country
Russian Federation
City
Vladivostok
Country
Russian Federation
City
Chernihiv
Country
Ukraine
City
Donetsk
Country
Ukraine
City
Kharkiv
Country
Ukraine
City
Kyiv
Country
Ukraine
City
Zaporizhia
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression
We'll reach out to this number within 24 hrs