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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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01529112
First received: January 6, 2012
Last updated: March 16, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Lenvatinib
Drug: Lenvatinib matched placebo
Drug: BSC
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Oral E7080 in Addition to Best Supportive Care (BSC) Versus BSC Alone in Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Who Have Failed at Least Two Systemic Anticancer Regimens

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Overall Survival (OS) [ 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 ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of randomization until the date of death from any cause.


Secondary Outcome Measures:
  • Number of Participants With Treatment Emergent Non-serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) [ 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) ] [ Designated as safety issue: Yes ]
    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.

  • 6-Month Survival Rate [ Time Frame: From date of randomization (Day 1) up to 6 months ] [ Designated as safety issue: No ]
    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.

  • 1-year Survival Rate [ Time Frame: From date of randomization (Day 1) up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Progression-Free Survival (PFS) [ Time Frame: From date of randomization (Day 1) until date of first documentation of disease progression or death from any cause (whichever occurred first) or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of the randomization until the date of first documented disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or date of death from any cause (whichever occurred first), assessed based on investigator's assessment. 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. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • Overall Response Rate (ORR) [ Time Frame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator using RECIST 1.1. 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 less than 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. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • Response Duration (RD) [ Time Frame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    Response duration, defined as the time from the date of the first assessment demonstrating a CR or PR to the date of the first assessment demonstrating progressive disease or death, whichever occurred first. This is an investigator assessed outcome, measured using RECIST 1.1. 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 less than 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. Response duration was summarized by including only subjects with events. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • Disease Control Rate (DCR) [ Time Frame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    The percentage of participants with CR, PR, or stable disease (SD) for greater than or equal to 12 weeks. 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 less than 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. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Symptom Scores Achieving Clinically Significant Deterioration on Quality of Life (QOL) [ Time Frame: Baseline (Day 1 of Cycle 1 (prior to treatment in Cycle 1)), every 4 weeks during treatment, and 4 weeks after completing treatment or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 symptom score, a cancer specific self-reporting questionnaire was composed of 9-symptom scales assessing fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. All of the multi-item scales and single-item measures ranged in score from 0 to 100. For each domain and item, a linear transformation was applied to standardize the raw score to a range from 0 to 100, with a higher scale score representing a higher response level/ high level of symptomatology / problems. The data is presented as percentage of participants with EORTC QLQ-C30 symptom score achieving clinically significant deterioration on QOL. Participants were considered as deteriorated for a given symptom if the change in score from Baseline was 10 points or higher at any time point after Baseline. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) Module QLQ-LC13 (Lung Cancer 13) Symptom Scores Achieving Clinically Significant Deterioration on QOL [ Time Frame: Baseline (Day 1 of Cycle 1 (prior to treatment in Cycle 1)), every 4 weeks during treatment, and 4 weeks after completing treatment or up to approximately 2 years (data cut-off date of 21 January 2014) ] [ Designated as safety issue: No ]
    The EORTC module QLQ-LC13 symptom score was a self-reporting cancer-specific questionnaire composed of 13 questions incorporated into 1 multi-item scale designed to evaluate dyspnea and a series of single items assessing different types of pain, as well as, cough, hemoptysis, dysphagia, sore mouth, alopecia, and peripheral neuropathy. For each domain and item, a linear transformation was applied to standardize the raw score to a range from 0 to 100, with 100 representing the best possible function/QOL, and highest burden of symptoms for symptom domains and single items. The data is presented as percentage of participants with EORTC module QLQ-C13 symptom score achieving clinically significant deterioration on QOL. Participants were considered as deteriorated for a given symptom if the change in score from Baseline was 10 points or higher at any time point after Baseline. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

  • Pharmacokinetic (PK) Profile of Lenvatinib in Subjects With Non Small Cell Lung Cancer (NSCLC) [ Time Frame: Cycle 1/Day 1 (between 0.5 and 4 hours postdose and 6 and 10 hours postdose), Cycle 1/Day 15 (predose, between 0.5 and 4 hours postdose, and 6 and 10 hours postdose), and Day 1 of Cycles 2 though 4 (predose and between 2 and 12 hours postdose) ] [ Designated as safety issue: No ]
    Blood samples were collected for lenvatinib PK analysis. Lenvatinib concentrations from sparse PK sampling were measured. The data is presented as mean nanograms per milliliter +/- Standard deviation of lenvatinib serum concentration.


Enrollment: 135
Study Start Date: November 2011
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenvatinib
Participants received lenvatinib 24 mg orally, once daily continuously in each 28-day treatment cycle plus Best Supportive Care (BSC)
Drug: Lenvatinib
Other Name: E7080
Drug: BSC
Placebo Comparator: Lenvatinib matched placebo
Participants received lenvatinib matched placebo orally, once daily continuously in each 28-day treatment cycle plus BSC
Drug: Lenvatinib matched placebo Drug: BSC

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01529112

  Show 50 Study Locations
Sponsors and Collaborators
Eisai Inc.
Quintiles, Inc.
Investigators
Study Director: Harish Dave PharmaBio Development Inc.
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01529112     History of Changes
Other Study ID Numbers: E7080-703 
Study First Received: January 6, 2012
Results First Received: February 17, 2016
Last Updated: March 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Locally Advanced
Metastatic Non-Squamous Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016