Clinical Trials /

Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung

NCT01877083

Description:

This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At least 20 subjects with KIF5B-RET will be treated and will receive lenvatinib at a starting dose of 24 mg orally, once per day. Additional subjects with other RET translocations will be treated with lenvatinib at a starting dose of 24 mg orally, once per day. The study will consist of 3 phases: The Pretreatment Phase, The Treatment Phase and the Extension Phase. The Pretreatment Phase will include screening procedures and eligibility assessments. The Pretreatment Phase consists of a Screen 1, Screen 2 and Baseline Period. The Treatment Phase will begin when the subject has met all eligibility criteria on Day 1 of the first Treatment Cycle. The Treatment Phase contains the Treatment and Follow-up Periods. The Extension Phase will begin for subjects who received treatment in the study (either in the Treatment Period or Follow-up Period) at the time of database cutoff.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Study of the Safety and Activity of <span class="go-doc-concept go-doc-intervention">Lenvatinib</span> (<span class="go-doc-concept go-doc-intervention">E7080</span>) in Subjects With <span class="go-doc-concept go-doc-biomarker">KIF5B</span>-<span class="go-doc-concept go-doc-biomarker">RET</span>-Positive Adenocarcinoma of the Lung

Title

  • Brief Title: Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung
  • Official Title: A Multicenter, Open-Label Phase 2 Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung
  • Clinical Trial IDs

    NCT ID: NCT01877083

    ORG ID: E7080-G000-209

    Trial Conditions

    KIF5B-RET-Positive Adenocarcinoma of the Lung

    Trial Interventions

    Drug Synonyms Arms
    Lenvatinib E7080 Lenvatinib

    Trial Purpose

    This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with
    KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At
    least 20 subjects with KIF5B-RET will be treated and will receive lenvatinib at a starting
    dose of 24 mg orally, once per day. Additional subjects with other RET translocations will
    be treated with lenvatinib at a starting dose of 24 mg orally, once per day. The study will
    consist of 3 phases: The Pretreatment Phase, The Treatment Phase and the Extension Phase.
    The Pretreatment Phase will include screening procedures and eligibility assessments. The
    Pretreatment Phase consists of a Screen 1, Screen 2 and Baseline Period. The Treatment Phase
    will begin when the subject has met all eligibility criteria on Day 1 of the first Treatment
    Cycle. The Treatment Phase contains the Treatment and Follow-up Periods. The Extension Phase
    will begin for subjects who received treatment in the study (either in the Treatment Period
    or Follow-up Period) at the time of database cutoff.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Lenvatinib Experimental Lenvatinib

    Eligibility Criteria

    Inclusion Criteria:

    1. Subjects must have a cytological or histological confirmed diagnosis of
    adenocarcinoma of the lung.

    2. Subject must be known to be RET positive (known KIF5B-RET translocation, or other
    confirmed RET translocations (e.g., CCDC6-RET)) or have an available tumor sample for
    local or central testing obtained prior to consent (Screen 1). Subjects whose samples
    need to be submitted for central laboratory testing must be current non-smokers and
    not known to have mutation in EGFR, KRAS, or ALK.

    3. Subjects may have received up to three prior systemic anticancer treatment regimens
    for adenocarcinoma of the lung (including adjuvant therapies and tyrosine-kinase
    inhibitors [TKI]), unless discussed with the sponsor.

    4. Subjects must have a clinically indicated need for systemic chemotherapy for
    adenocarcinoma of the lung based on the investigator's assessment

    5. Presence of measurable disease meeting the following criteria:

    1. At least one lesion of at least 1.0 cm in the long-axis diameter for a non-lymph
    node or at least 1.5 cm in the short-axis diameter for a lymph node which is
    serially measurable according to Response Evaluation Criteria in Solid Tumors
    1.1 (RECIST 1.1) using either computerized tomography (CT) or magnetic resonance
    imaging (MRI). If there is only one target lesion and it is a non-lymph node, it
    should have a longest diameter of at least 1.5 cm.

    2. Lesions previously treated with radiotherapy or locoregional therapy must show
    radiographic evidence of disease progression to be deemed a target lesion.

    6. Subjects with known brain metastases who have completed whole brain radiotherapy,
    stereotactic radiosurgery, or complete surgical resection will be eligible if they
    have remained clinically stable, asymptomatic and off of steroids for 28 days.

    7. Adequate bone marrow function, defined as:

    1. Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L (greater
    than or equal to 1500/mm^3)

    2. Hemoglobin (Hb) greater than or equal 8.5 g/dL

    3. Platelet count greater than or equal 75 x 10^9/L (greater than or equal
    75,000/mm^3)

    8. Adequate liver function, defined as:

    1. Bilirubin less than or equal 1.5 x upper limit of normal (ULN) except for
    unconjugated hyperbilirubinemia or Gilbert's syndrome

    2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline
    phosphatase (ALP) less than or equal 3 x ULN (less than or equal 5 x ULN if
    subject has liver metastases). If alkaline phosphatase is greater than 3 x ULN
    (in absence of liver metastases) or greater than 5 x ULN (in presence of liver
    metastases) AND the subject also is known to have bone metastases, the
    liver-specific alkaline phosphatase must be separated from the total and used to
    assess the liver function instead of total alkaline phosphatase.

    9. Adequate renal function, defined as calculated creatinine clearance greater than 40
    mL/min per the Cockcroft and Gault formula.

    10. Adequately 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 before Cycle 1/Day 1 (C1D1).

    11. Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 0 or 1.

    12. Survival expectation of 12 weeks or longer after starting study drug.

    13. Males or females aged at least 18 years (or any age greater than 18 years as
    determined by country legislation) at the time of informed consent (Screen 1).

    14. Females must not be breast-feeding or pregnant at Screening or Baseline (as
    documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a
    minimum sensitivity of 25 IU/L or equivalent units of B-hCG). A separate baseline
    assessment is required if a negative Screening pregnancy test was obtained more than
    72 hours before the first dose of study drug.

    15. All females will be considered to be of childbearing potential unless they are
    postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate
    age group and without other known or suspected cause) or have been sterilized
    surgically (i.e., bilateral tubal ligation, total hysterectomy or bilateral
    oophorectomy, all with surgery at least one month before dosing).

    16. Females of childbearing potential must not have had unprotected sexual intercourse
    within 30 days before study entry and must agree to use a highly effective method of
    contraception (e.g., total abstinence, an intrauterine device, a double-barrier
    method [such as condom plus diaphragm with spermicide], a contraceptive implant, an
    oral contraceptive, or have a vasectomized partner with confirmed azoospermia)
    throughout the entire study period and for 30 days after study drug discontinuation.
    If currently abstinent, the subject must agree to use a double barrier method as
    described above if she becomes sexually active during the study period or for 30 days
    after study drug discontinuation. Females who are using hormonal contraceptives must
    have been on a stable dose of the same hormonal contraceptive product for at least 4
    weeks before dosing and must continue to use the same contraceptive during the study
    and for 30 days after study drug discontinuation.

    17. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they
    and their female partners must meet the criteria above (i.e., not of childbearing
    potential or practicing highly effective contraception throughout the study period
    and for 30 days after study drug discontinuation). No sperm donation is allowed
    during the study period and for 30 days after study drug discontinuation.

    18. Provide written informed consent (Screen 1 and Screen 2)

    19. Willing and able to comply with all aspects of the protocol

    Exclusion Criteria:

    1. Subjects who have received any anticancer therapy (including surgery, locoregional,
    biological, immunotherapy, hormonal, or radiotherapy) within 21 days before the first
    dose of study drug (28 days for investigational therapies).

    2. Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.

    3. Subjects who have not recovered from toxicities as a result of prior anticancer
    therapy to less than Grade 2 severity per the National Cancer Institute Common
    Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and
    infertility.

    4. Significant cardiovascular impairment: history of congestive heart failure greater
    than New York Heart Association (NYHA) Class II, unstable angina, myocardial
    infarction, or stroke within 6 months of the first dose of study drug, or cardiac
    arrhythmia requiring medical treatment at Screening.

    5. Gastrointestinal malabsorption or any other condition in the opinion of the
    investigator that might affect the absorption of lenvatinib.

    6. Active malignancy (except for adenocarcinoma of the lung or definitively treated
    melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ
    of the cervix) within the past 24months.

    7. Major surgery within 3 weeks before the first dose of study drug.

    8. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar
    agents requiring therapeutic international normalized ratio (INR) monitoring.
    (Treatment with low molecular weight heparin is allowed.)

    9. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before
    the first dose of study drug.

    10. Active infection (any infection requiring treatment).

    11. Symptomatic central nervous system (CNS) disease.

    12. Subjects having greater than 1+ proteinuria on urine dipstick testing will undergo
    24-hour urine collection for quantitative assessment of proteinuria. Subjects with
    urine protein greater than or equal to 1 g/24-hour will be ineligible.

    13. Any medical or other condition that in the opinion of the investigator(s) would
    preclude the subject's participation in a clinical study or would preclude them from
    completing the study.

    14. Scheduled for surgery during the study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate (ORR)

    Secondary Outcome Measures

    Progression free survival (PFS)

    Overall survival (OS)

    Trial Keywords

    KIF5B-RET-Positive Adenocarcinoma

    Lung Cancer

    NSCLC

    Non-Small Cell Lung Cancer