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

Eisai Inc.135 enrolled

Overview

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.

This double-blind, placebo-controlled, multicenter, randomized Phase II study will consist of a 2-arm design, comparing E7080 + BSC (Arm 1) with placebo + BSC (Arm 2). Participants will be randomized in the ratio of 2:1 to receive either E7080 or placebo in a blinded manner.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

135

Conditions

Non-Small Cell Lung Cancer

Interventions

LenvatinibDRUG

Lenvatinib matched placeboDRUG

BSCDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (50)

Outcomes

Primary Outcomes

Overall Survival (OS)

OS was defined as the time from the date of randomization until the date of death from any cause.

Time frame: From date of randomization (Day 1) until occurrence of 90 deaths in the study (cut off date 26 November 2013), approximately 22 months

Secondary Outcomes

Number of Participants With Treatment Emergent Non-serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A SAE was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (i.e., the subject was at a risk of death at the time of the event; this did not include an event that hypothetically might have caused death if it had been more severe), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital abnormality/birth defect. In this study, treatment emergent adverse events (TEAEs) (defined as an AE (serious/non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.

Time frame: For each participant, from the first dose till 30 days after the last dose or up to approximately 2 years (data cut-off date of 21 January 2014)

6-Month Survival Rate

Event-free survival rate was calculated using Kaplan Meier estimations. The percentage of participants with event free survival up to 6 months and the corresponding 95% confidence interval were estimated for each treatment group. The data presented is based on the data cut-off date of 26 November 2013 while the study is still ongoing.

Time frame: From date of randomization (Day 1) up to 6 months

1-year Survival Rate

Event-free survival rate was calculated using Kaplan Meier estimations. The percentage of participants with event free survival up to 1 year and the corresponding 95% confidence interval were estimated for each treatment group. The data presented is based on the data cut-off date of 26 November 2013 while the study is still ongoing.

Data from ClinicalTrials.gov

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