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

NCT ID: NCT02422589

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-23

Study Completion Date

2017-12-12

Brief Summary

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The purpose of this study was 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 would provide guidance that would enable an update to the ceritinib labeling and ouldl help guide recommendations for administration of co-medications in future clinical trials.

Detailed Description

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Conditions

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ALK-positive Advanced Tumors

Keywords

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ALK-positive advanced tumors midazolam warfarin ceritinib ALK CYP3A-4 Drug drug intereaction

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Ceritinib

Group Type EXPERIMENTAL

ceritinib

Intervention Type DRUG

warfarin

Intervention Type DRUG

midazolam

Intervention Type DRUG

Interventions

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ceritinib

Intervention Type DRUG

warfarin

Intervention Type DRUG

midazolam

Intervention Type DRUG

Eligibility Criteria

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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 1.In case last chemotherapy contained nitrosourea or mitomycin C, the treatment was discontinued at least 6 weeks prior to starting study drug.
* 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), such as:
* Unstable angina within 6 months prior to screening.
* Myocardial infarction within 6 months prior to screening.
* History of documented congestive heart failure (New York Heart Association functional classification III-IV).
* Uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mmHg and/or Diastolic Blood Pressure ≥ 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication (s) was allowed prior to screening.
* Ventricular arrhythmias.
* Supraventricular and nodal arrhythmias not controlled with medication.
* Other cardiac arrhythmia not controlled with medication.
* Corrected QT (QTcF) \> 470 ms using Fridericia's correction on the screening electrocardiogram (ECG) (as mean of triplicate ECGs).
* 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 applied.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Karmanos Cancer Institute Oncology Department

Detroit, Michigan, United States

Site Status

Henry Ford Hospital SC

Detroit, Michigan, United States

Site Status

Cancer Therapy & Research Center UT Health Science Center SC-4

San Antonio, Texas, United States

Site Status

Novartis Investigative Site

Copenhagen, , Denmark

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Modena, MO, Italy

Site Status

Novartis Investigative Site

Padua, PD, Italy

Site Status

Novartis Investigative Site

A Coruña, Galicia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Countries

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Germany United States Denmark Italy Spain

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17277

Results for CLDK378A2103 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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2014-003741-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDK378A2103

Identifier Type: -

Identifier Source: org_study_id