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

NCT01111461 | Completed Phase 2 Results

• 1 other identifier: E7080-G000-204
• Study Type: interventional
• Target: 133
• Locations: 8 countries
• Sites: 78

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. .

Conditions

Endometrial Cancer

Keywords

Advanced Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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 (5)

• Progression Free Survival (PFS)

  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)

• Overall Survival (OS)

  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)

• Disease Control Rate (DCR)

  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)

• Clinical Benefit Rate (CBR)

  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)

• Number of Participants With Adverse Events (AEs) /Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib Tolerability of Lenvatinib

  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 (4)

• Summary of Plasma Concentration of Lenvatinib

  Predose and 2 hours postdose on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1

• 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

  Cycle 1 Day 5

• Percentage Change From Baseline in the Contrast Volume Transfer Coefficient (Ktrans) Median

  Cycle 1 Day 5

Study Arms (1)

Lenvatinib 24 mg

EXPERIMENTAL

Participants with advanced endometrial cancer and disease progression following platinum-based, first line chemotherapy.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

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.

Also known as: E7080, Lenvima

Lenvatinib 24 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (78)

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Los Angeles, California, United States

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Honolulu, Hawaii, United States

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Arlington Heights, Illinois, United States

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Niles, Illinois, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Burnsville, Minnesota, United States

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Edina, Minnesota, United States

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Maplewood, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Paul, Minnesota, United States

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Woodbury, Minnesota, United States

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St Louis, Missouri, United States

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Morristown, New Jersey, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cleveland, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Eugene, Oregon, United States

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Portland, Oregon, United States

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Springfield, Oregon, United States

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Tualatin, Oregon, United States

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Charleston, South Carolina, United States

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Austin, Texas, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Tyler, Texas, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Vancouver, Washington, United States

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Arlon, Belgium

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Charleroi, Belgium

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Duffel, Belgium

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Ghent, Belgium

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Kortrijk, Belgium

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Leuven, Belgium

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Liège, Belgium

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Namur, Belgium

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Ostend, Belgium

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Roeselare, Belgium

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Yvoir, Belgium

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Veliko Tarnovo, Bulgaria

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Budapest, Hungary

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Győr, Hungary

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Lublin, Poland

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Poznan, Poland

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Warsaw, Poland

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Brasov County, Romania

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Bucharest, Romania

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Cluj County, Romania

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Dolj County, Romania

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Kazan', Russia

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Nizhny Novgorod, Russia

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Orenburg, Russia

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Pyatigorsk, Russia

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Saint Petersburg, Russia

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Sochi, Russia

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Stavropol, Russia

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Syktyvkar, Russia

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Tomsk, Russia

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Tula, Russia

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Ufa, Russia

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Vladivostok, Russia

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Chernihiv, Ukraine

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Donetsk, Ukraine

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Zaporizhia, Ukraine

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MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

18884224743

Study Officials

• Eisai Medical Services

  Eisai Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2010
• First Posted: April 27, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: October 1, 2015
• Last Updated: June 22, 2023
• Results First Posted: April 18, 2016

Record last verified: 2016-11

Locations

UA (5); HU (2); RO (4); RU (12); US (36); PL (3); BE (11); BU (5)