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A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors

NCT02422589

Description:

The purpose of this study is to evaluate the potential inhibitory effects of ceritinib on the CYP3A4- and CYP2C9-mediated metabolism of the probe drugs midazolam and warfarin, respectively, when administered simultaneously as a cocktail. The results obtained from this drug interaction study will provide guidance that will enable an update to the ceritinib labeling and will help guide recommendations for administration of co-medications in future clinical trials.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of <span class="go-doc-concept go-doc-intervention">Ceritinib</span> on the Pharmacokinetics of <span class="go-doc-concept go-doc-intervention">Warfarin</span> and <span class="go-doc-concept go-doc-intervention">Midazolam</span> in Patients With <span class="go-doc-concept go-doc-biomarker">ALK</span>-positive Advanced Tumors

Title

  • Brief Title: A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors
  • Official Title: A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam Administered as a Two-drug Cocktail in Patients With ALK-positive Advanced Tumors Including Non-small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02422589

    ORG ID: CLDK378A2103

    NCI ID: 2014-003741-95

    Trial Conditions

    ALK-positive Advanced Tumors

    Trial Interventions

    Drug Synonyms Arms
    ceritinib Ceritinib
    warfarin Ceritinib
    midazolam Ceritinib

    Trial Purpose

    The purpose of this study is to evaluate the potential inhibitory effects of ceritinib on
    the CYP3A4- and CYP2C9-mediated metabolism of the probe drugs midazolam and warfarin,
    respectively, when administered simultaneously as a cocktail. The results obtained from
    this drug interaction study will provide guidance that will enable an update to the
    ceritinib labeling and will help guide recommendations for administration of co-medications
    in future clinical trials.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Ceritinib Experimental ceritinib, warfarin, midazolam

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a
    candidate for definitive multimodality therapy) or stage IV NSCLC demonstrated
    ALK-positive or an advanced tumor, other than NSCLC, that carries an ALK genetic
    alteration (mutation, translocation or amplification) and/or ALK overexpression that
    has progressed despite standard therapy, or for which no effective standard therapy
    exists.

    - The test to confirm ALK-positivity may be performed in archival tumor (obtained at or
    since the time of diagnosis), or in a newly obtained tumor sample taken prior to the
    first day of study drug. Results confirming ALK-positive status must be available
    before initiating treatment with ceritinib.

    - Patients who have received prior chemotherapy, other ALK inhibitors, biologic
    therapy, or other investigational agents, must have recovered from all toxicities
    related to prior anticancer therapies to grade 1 (CTCAE v 4.03) prior to starting
    study drug. Patients with grade 2 peripheral neuropathy or any grade of alopecia,
    nail changes or skin changes are allowed to enter the study.

    - Patients who have been treated with chemotherapy, with biological therapy or other
    investigational agent must have discontinued the treatment at least 2 weeks (14 days)
    prior to starting the study drug on Study Day -

    - Patient has the ability to understand and provide signed informed consent.

    Exclusion Criteria:

    - Patients with known hypersensitivity to any of the excipients of ceritinib
    (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and
    magnesium stearate), midazolam and warfarin as described in the local product
    information.

    - History of carcinomatous meningitis.

    - Presence or history of a malignant disease other than an ALK-positive advanced tumor
    that has been diagnosed and/or required therapy within the past 3 years. Exceptions
    to this exclusion include the following: completely resected basal cell and squamous
    cell skin cancers, and completely resected carcinoma in situ of any type.

    - Clinically significant, uncontrolled heart disease and/or recent cardiac event
    (within 6 months

    - Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) 160 mmHg
    and/or Diastolic Blood Pressure (DBP) 100 mmHg, with or without anti-hypertensive
    medication.

    - Patient has history of interstitial lung disease or interstitial pneumonitis,
    including clinically significant radiation pneumonitis (i.e., affecting activities of
    daily living or requiring therapeutic intervention).

    - Other Protocol defined Inclusion/Exclusion may apply.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phamacokinetics (PK) parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not limited to: AUCinf

    PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to: AUC

    PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Cmax

    PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Tmax

    Secondary Outcome Measures

    Ctrough concentrations of ceritinib

    Number of participants with Adverse Events as a measure of safety and tolerability

    Objective Response Rate (ORR)

    Duration of Response (DOR)

    Trial Keywords

    ALK-positive advanced tumors,

    midazolam,

    warfarin,

    ceritinib,

    ALK,

    CYP3A-4,

    Drug drug intereaction