Clinical Trials /

A Study of BGB324 in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer

NCT02424617

Description:

A Phase I/2 multi-center open-label study of BGB324 in combination with erlotinib in patients with Stage IIIb or Stage IV non-small cell lung cancer. BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor which is connected with poor prognosis and acquired resistance to therapy.

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

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">BGB324</span> in Combination With <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Patients With Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: A Study of BGB324 in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer
  • Official Title: A Multi-Center Open-Label Phase I Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02424617

    ORG ID: BGBC004

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    erlotinib Tarceva Arm A, Arm B, Arm C
    BGB324 Arm A, Arm B, Arm C

    Trial Purpose

    A Phase I/2 multi-center open-label study of BGB324 in combination with erlotinib in
    patients with Stage IIIb or Stage IV non-small cell lung cancer.

    Detailed Description

    This is a multi-center, multi-arm open-label Phase I/2 study that will be conducted at up to
    4 clinical sites in the US.

    Up to approximately 66 patients with histologically- or cytologically-confirmed Stage IIIb
    or Stage IV non-small cell lung cancer will receive BGB324 as a single agent (Run-in Cohort)
    or in combination with erlotinib (Arms A-C).

    The dose of erlotinib will be 150 mg daily (Arms A - C). A dose of 100 mg daily will be
    permitted in Arms B and C only. In Arm A, the dose of BGB324 will be escalated in a standard
    3+3 fashion until an MTD of the combination is established. At this point, Arm B and Arm C
    will be initiated. It is intended that the BGB324 MTD dose observed in Arm A will be used
    in Arms B and C, but a lower dose level may be incorporated upon recommendation of the
    Safety Review Committee. Dose escalation beyond the Arm A MTD level is not planned for Arm
    B or Arm C.

    Trial Arms

    Name Type Description Interventions
    Arm A Active Comparator designed to determine the maximum dose of BGB324 that can be safely administered in combination with erlotinib administered at the approved oral dose level of 150 mg daily. It is anticipated that a maximum of three BGB324 dose levels will be evaluated, with up to approximately 18 patients enrolled. In the absence of unacceptable toxicity, patients will be allowed to continue receiving BGB324 in combination with erlotinib until disease progression. erlotinib, BGB324
    Arm B Active Comparator will incorporate a Simon-like two-stage design with relaxed stopping for futility to evaluate the safety, pharmacokinetics and clinical activity of BGB324 in combination with erlotinib in patients with an activating EGFR mutation who have progressed after receiving prior erlotinib. erlotinib, BGB324
    Arm C Active Comparator will evaluate the safety, pharmacodynamics and clinical activity of BGB324 when administered in combination with erlotinib in patients with an activating EGFR mutation who have received at least twelve weeks of erlotinib without disease progression. erlotinib, BGB324

    Eligibility Criteria

    Inclusion Criteria:

    - Provision of written informed consent to participate in this investigational study

    - Histological or cytological confirmation of Stage IIIb or Stage IV (unresectable)
    NSCLC

    - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    - Age 18 years or older

    - Known EGFR mutation status

    - Has been receiving full dose erlotinib for treatment of NSCLC for at least six weeks
    with erlotinib-related toxicities being well-controlled and less than Grade 3 in
    severity at screening and is scheduled to continue treatment with erlotinib

    - Female patients of childbearing potential must have a negative serum pregnancy test
    within 7 days prior to taking their first dose of BGB324. Male patients and female
    patients of reproductive potential must agree to practice highly effective methods of
    contraception (such as hormonal implants, combined oral contraceptives, injectable
    contraceptives, intrauterine device with hormone spirals, total sexual abstinence,
    vasectomy) throughout the study and for 3 months after the last dose of BGB324.
    Female patients are considered NOT of childbearing potential if they have a history
    of surgical sterility, including tubal ligation, or evidence of post-menopausal
    status defined as any of the following:

    - Natural menopause with last menses >1 year ago

    - Radiation induced oophorectomy with last menses >1 year ago

    - Chemotherapy induced menopause with last menses >1 year ago

    Exclusion Criteria:

    - Pregnant or lactating

    - Abnormal left ventricular ejection fraction (less than the lower limit of normal for
    a patient of that age at the treating institution or <45%)

    - Treatment with any of the following: histamine receptor two inhibitors, protocol pump
    inhibitors or antacids within three days or five half-lives, whichever is longer

    - History of an ischemic cardiac event including myocardial infarction within 3 months
    of study entry

    - NSCLC with evidence of a centrally cavitating lesion

    - Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within six weeks unless cause has
    been addressed and is medically resolved

    - Treatment with cytotoxic chemotherapy within the preceding four weeks

    - Treatment with other non-cytotoxic agents for NSCLC in the preceding ten days or four
    terminal half-lives, whichever is shorter

    - Congestive cardiac failure of >Grade 2 severity according to the NYHA defined as
    symptomatic at less than ordinary levels of activity

    - Unstable cardiac disease, including unstable angina or unstable hypertension, as
    defined by the need for change in medication for lack of disease control within the
    last three months

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    History of an ischemic cardiac event including myocardial infarction

    Secondary Outcome Measures

    Trial Keywords