Clinical Trials /

Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.

NCT02292550

Description:

This is a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer. The purpose of the study is to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination is safe and has beneficial effects in ALK-positive advanced non-small cell lung cancer patients.

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

Completed

Phase:

Phase 1

Trial Eligibility

Document

Study of Safety and Efficacy of LEE011 and <span class="go-doc-concept go-doc-intervention">Ceritinib</span> in Patients With <span class="go-doc-concept go-doc-biomarker">ALK</span>-positive Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>.

Title

  • Brief Title: Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.
  • Official Title: A Phase Ib/II Study of the ALK Inhibitor Ceritinib in Combination With the CDK4/6 Inhibitor LEE011 in Patients With ALK-positive Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02292550

    ORG ID: CLEE011X2110C

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    LEE011 ribociclib Group A, Group B, Group C
    Ceritinib LDK378, Zykadia Group A, Group B, Group C

    Trial Purpose

    This is a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6
    inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer.

    The purpose of the study is to determine the MTD/RP2D of the LEE011 and ceritinib
    combination and evaluate whether the combination is safe and has beneficial effects in
    ALK-positive advanced non-small cell lung cancer patients.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Group A Experimental Patients naive to treatment with any ALK inhibitor LEE011, Ceritinib
    Group B Experimental Patients who have progressed after treatment with an ALK inhibitor other than ceritinib LEE011, Ceritinib
    Group C Experimental Patients who have progressed after treatment with ceritinib LEE011, Ceritinib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be
    ALK-positive as determined by ALK rearrangement in 15% of cells (as measured by FISH
    using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The
    analysis may be performed locally.

    - Eastern cooperative oncology group (ECOG) performance status 2.

    - Measurable disease as per RECIST v1.1

    - Availability of tumor sample:

    For ALK inhibitor nave patients:

    o A representative tumor sample must be submitted. An archival tumor specimen is
    acceptable

    For patients after progression on an ALK inhibitor:

    o A new tumor biopsy is required unless a biopsy performed after progression on the
    patient's most recent ALK inhibitor is available for submission For all patients a newly
    obtained tumor specimen must be submitted if no appropriate archival sample is available.
    In the event that no sample is available and a new biopsy cannot be obtained, enrollment
    may be considered after discussion with the sponsor.

    Exclusion Criteria:

    - For Phase II part:

    - Group A: prior therapy with any ALK inhibitor is not permitted.

    - Group B: progression following any ALK inhibitor(s) other than ceritinib is
    required and the last dose of the ALK inhibitor must be no more than 60 days
    prior to the first dose of study drug. Prior ceritinib is not permitted.

    - Group C: progression following ceritinib is required and the last dose of
    ceritinib must be no more than 60 days prior to the first dose of study drug.

    - Patients who have previously received ceritinib must have tolerated a dose of
    ceritinib 600 mg QD, or greater.

    - Patients with symptomatic central nervous system (CNS) metastases who are
    neurologically unstable or require increasing doses of steroids or local CNS-directed
    therapy to control their CNS disease

    - Impaired cardiac function or any clinically significant cardiac disease

    - Patients with abnormal laboratory values during screening and on day 1 of pre-dose

    - Impairment of gastrointestinal (GI) function or GI disease that may significantly
    alter the absorption of ceritinib or LEE011

    - Patients who are currently receiving treatment (that cannot be discontinued at least
    1 week prior to the initiation of the study) with agents that are known to be any of
    the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of
    CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index.

    - Patient has a history of pancreatitis or history of increased amylase or lipase that
    was due to pancreatic disease.

    Other protocol-defined inclusion/exclusion criteria may apply.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib )

    Overall Response Rate (ORR) as per RECIST v1.1

    Exposure to LEE011 and ceritinib (Phase Ib )

    Secondary Outcome Measures

    Overall Response Rate (ORR) - Phase Ib & II

    Frequency of adverse events/serious adverse events

    PK parameters of LEE011 and ceritinib

    Frequency of dose interruptions and dose reductions (phase lb & ll)

    Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II

    Duration of response (DOR)

    Time to response (TTR) - Phase Ib & II

    Disease Control Rate (DCR) - Phase Ib & II

    Overall survival (OS) - Phase Ib & II

    Severity of adverse events/serious adverse events

    Trial Keywords

    Non-small cell lung cancer,

    ALK translocation,

    ALK-positive,

    NSCLC,

    LEE011,

    CDK4/6 inhibitor,

    EML4-ALK