Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01111461
First received: April 16, 2010
Last updated: April 7, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to assess the objective response rate of lenvatinib in participants with advanced endometrial cancer and disease progression following platinum-based, first line chemotherapy.

Condition Intervention Phase
Endometrial Cancer
Drug: Lenvatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ 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) ] [ Designated as safety issue: No ]
    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 using MRI/CT scans, as determined by independent radiologic review (IRR). A BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. A 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 (whether target or non-target) had to have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR=CR + PR.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ 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 2.3 years (as of 21 May 2012 data cut-off) ] [ Designated as safety issue: No ]
    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 IRR and Investigator based on Response Evaluation Criteria In Solid Tumors (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) [ Time Frame: From date of first administration of study treatment until the date of death or up to approximately 2.3 years (as of 21 May 2012 data cut-off) ] [ Designated as safety issue: No ]
    OS was the length time in months from the date of first treatment until the date of death from any cause or approximately 2.3 years (as of 21 May 2012 data cut-off).

  • Disease Control Rate (DCR) [ 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 2.3 years (as of 21 May 2012 data cut-off) ] [ Designated as safety issue: No ]
    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 seven weeks, as determined by IRR and Investigator.

  • Clinical Benefit Rate (CBR) [ 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 2.3 years (as of 21 May 2012 data cut-off) ] [ Designated as safety issue: No ]
    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 durable SD (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 [ Time Frame: For each participant, from the first patient first dose till 30 days after the last dose of study treatment or the cut-off date for the primary analysis, whichever was earlier, up to approximately 2.3 years. ] [ Designated as safety issue: Yes ]
    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.

  • Pharmacokinetic (PK) Profile and Pharmacodynamics (PD) of Lenvatinib [ Time Frame: On Cycle 1 Day 1, Cycle 1 Day 8 and the Cycle 2 Day 1 ] [ Designated as safety issue: Yes ]
    Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors. For PD, change from baseline in serum biomarkers was analyzed.


Enrollment: 133
Study Start Date: March 2010
Study Completion Date: October 2015
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenvatinib 24 mg
Participants with advanced endometrial cancer and disease progression following platinum-based, first line chemotherapy.
Drug: Lenvatinib
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.
Other Name: E7080

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111461

  Show 79 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Principal Investigator: Eisai US Medical Services
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01111461     History of Changes
Other Study ID Numbers: E7080-G000-204 
Study First Received: April 16, 2010
Results First Received: March 13, 2015
Last Updated: April 7, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Advanced Endometrial Cancer

Additional relevant MeSH terms:
Disease Progression
Endometrial Neoplasms
Disease Attributes
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Pathologic Processes
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Lenvatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 30, 2016