Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression
Condition: Endometrial Cancer
MeSH terms: Endometrial Neoplasms; Disease Progression
Intervention: Lenvatinib
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.
Intervention MeSH terms: Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 133.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Endometrial Cancer

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.