A Study Comparing the Combination of the Best Supportive Care Plus E7080 Versus Best Supportive Care Alone, in Patients With Advanced Lung Cancer or Lung Cancer That Has Spread, Who Have Been Previously Treated, Unsuccessfully, With at Least 2 Different Treatments
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Lenvatinib; Lenvatinib matched placebo; BSC
Intervention MeSH terms: Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 135.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Locally Advanced; Metastatic Non-Squamous Non-Small Cell Lung Cancer

Summary:

      The purpose of this study is to compare the overall survival of patients receiving E7080 +
      Best Supportive Care (BSC) with those receiving placebo + Best Supportive Care.
    

Eligibility criteria:

        Inclusion Criteria

          1. Age greater than or equal to 18 years;

          2. Participants with histologically or cytologically confirmed non-squamous NSCLC with
             locally advanced or metastatic disease based on Tumor, Node, Metastasis (TNM) staging
             according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual,
             Seventh Edition, who had failed at least two lines of systemic anticancer therapy for
             advanced or metastatic NSCLC (did not include adjuvant chemotherapy). In countries
             where erlotinib was approved and marketed for the treatment of NSCLC, participants
             must have received erlotinib treatment (or gefitinib for participants outside of the
             US) for their NSCLC if they had known EGFR-activating mutations. Participants of
             unknown EGFR status who had not received prior erlotinib (or gefitinib) should have
             been tested for EGFR-activating mutations prior to study entry. In countries where
             crizotinib was approved and marketed, participants must have received crizotinib
             treatment for NSCLC that was ALK-positive. Participants with ALK positive NCSLC or
             participants with KRAS mutations were not required to have prior treatment with
             erlotinib or gefitinib

          3. Participants must have at least 1 site of measurable disease by the Response
             Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1);

          4. ECOG PS of 0 to 2;

          5. Participants must have adequate renal function as evidenced by serum creatinine less
             than or equal to 1.5 x upper limit of normal (ULN) or calculated creatinine clearance
             greater than or equal to 30 mL/min per the Cockcroft and Gault formula;

          6. Blood pressure must be well-controlled (less than or equal to140/90 mm Hg at
             Screening) with or without antihypertensive medication. Participants must have no
             history of hypertensive crisis or hypertensive encephalopathy;

          7. Participants must have adequate bone marrow function as evidenced by absolute
             neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than
             or equal to 9.0 g/dL, and platelet count greater than or equal to 100 x 109/L;

          8. Participants must have adequate liver function as evidenced by bilirubin less than or
             equal to 1.5 times the ULN, and alkaline phosphatase, alanine aminotransferase (ALT),
             and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of
             liver metastases, less than or equal to 5 x ULN).

          9. Participants must have adequate coagulation system function as defined by prothrombin
             time/International normalized ratio (INR) less than or equal to 1.5 x ULN.

         10. Male or female participants of child-producing potential must agree to use double
             barrier contraception, oral contraceptives, or avoidance of pregnancy measures during
             the study and for 90 days after the last day of treatment;

         11. Females of childbearing potential must have a negative serum pregnancy test;

         12. Females may not be breastfeeding;

         13. Ability to understand and willingness to sign a written informed consent.

        Exclusion Criteria

          1. Prior therapy with E7080 or other small molecule vascular endothelial growth factor
             inhibitors;

          2. Presence of brain metastases, unless the participant has received adequate treatment
             at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids
             for at least 4 weeks prior to randomization;

          3. Meningeal carcinomatosis;

          4. Received chemotherapy, targeted therapy, radiotherapy, surgery, or immunotherapy
             within the 21 days prior to commencing study treatment or have not recovered from all
             treatment-related toxicities to Grade less than or equal to 2, except for alopecia;

          5. Received treatment with another investigational agent within the 30 days prior to
             commencing study treatment or participants who have not recovered from side effects of
             an investigational drug to Grade less than or equal to 2, except for alopecia;

          6. Participants with proteinuria greater than 1+ on urine dipstick testing will undergo
             24-hour urine collection for quantitative assessment of proteinuria. Participants with
             24-hour urine protein greater than or equal to 1 g/24 hours will be ineligible;

          7. Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical
             procedure, open biopsy, or significant traumatic injury within the 28 days prior to
             commencing study treatment.

          8. Major surgery scheduled during the projected course of the study;

          9. History of bleeding diathesis or coagulopathy;

         10. Active hemoptysis (defined as bright red blood of a half teaspoon or more) within the
             30 days prior to study entry;

         11. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any
             other medical condition that would preclude adequate absorption or result in the
             inability to take oral medication;

         12. Other malignancy within 3 years of randomization, with the exception of adequately
             treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no
             subsequent evidence of recurrence and/or malignancies diagnosed at a stage where
             definitive therapy results in near certain cures.

         13. Significant cardiovascular impairment (history of congestive heart failure New York
             Heart Association [NYHA] Class greater than II, unstable angina or myocardial
             infarction within the past 6 months, or serious cardiac arrhythmia);

         14. Any history of cerebral vascular accident (CVA), transient ischemic attack (TIA), or
             Grade greater than or equal to 2 peripheral vascular disease unless they have had no
             evidence of active disease for at least 6 months prior to randomization;

         15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within the 6 months prior to enrollment;

         16. Participants with organ allografts requiring immunosuppression;

         17. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen,
             or hepatitis C positive;

         18. Hypersensitivity to E7080 or any of the excipients;

         19. Any history of or concomitant medical condition that, in the opinion of the
             Investigator, would compromise the participant's ability to safely complete the study.