Clinical trial NCT01111461: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Advanced Endometrial Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-04-27
Enrollment: 133
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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. .


Eligibility criteria: Inclusion criteria:

1. Histologically confirmed diagnosis of endometrial carcinoma.
2. 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.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status less than 2.
5. 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.
6. Adequate renal function defined as calculated creatinine clearance greater than 30 mL/min per the Cockcroft and Gault formula.
7. Adequate bone marrow, blood coagulation, and liver functions, as defined in the study protocol.
8. Negative serum or urine pregnancy test for women of reproductive potential.

Exclusion criteria:

1. Brain or leptomeningeal metastases, including stable metastases.
2. 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.
3. Prior systemic anti-tumor therapy within 3 weeks.
4. Not fully recovered from prior radiotherapy based on investigator judgement.
5. 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.
6. 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.
7. Prolongation of QTc interval greater than 480 msec.
8. 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).
9. Active hemoptysis within 3 weeks prior to the first dose of study drug.
10. Females who are pregnant or breast feeding.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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 outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: 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)
measure: Clinical Benefit Rate (CBR)
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib
timeFrame: 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 outcomes:
measure: Summary of Plasma Concentration of Lenvatinib
timeFrame: Predose and 2 hours postdose on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1
measure: 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
timeFrame: Cycle 1 Day 5
measure: Percentage Change From Baseline in the Contrast Volume Transfer Coefficient (Ktrans) Median
timeFrame: Cycle 1 Day 5
measure: Percentage Change From Baseline in the Apparent Diffusion Coefficient (ADC) Median
timeFrame: Cycle 1 Day 5
Locations:
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Honolulu
country: United States
state: Hawaii
city: Arlington Heights
country: United States
state: Illinois
city: Niles
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Burnsville
country: United States
state: Minnesota
city: Edina
country: United States
state: Minnesota
city: Maplewood
country: United States
state: Minnesota
city: Minneapolis
country: United States
state: Minnesota
city: Saint Paul
country: United States
state: Minnesota
city: Woodbury
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Morristown
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cleveland
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Springfield
country: United States
state: Oregon
city: Tualatin
country: United States
state: Oregon
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Vancouver
country: United States
state: Washington
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
Study officials:
affiliation: Eisai Limited
name: Eisai Medical Services
role: STUDY_DIRECTOR
References: