Pharmacokinetic and Safety Study of Lower Doses of Ceritinib Taken With a Low-fat Meal Versus 750 mg of Ceritinib in the Fasted State in Adult Patients With (ALK-positive) Metastatic Non-small Cell Lung Cancer (NSCLC)

February 7, 2022 updated by: Novartis Pharmaceuticals

A Multi-center, Randomized Open Label Study to Assess the Systemic Exposure, Effiacy, and Safety of 450 mg Ceritinib Taken With a Low-fat Meal and 600 mg Ceritinib Taken With a Low-fat Meal as Compared With That of 750 mg Ceritinib Taken in the Fasted State in Adult Patients With ALK Rearranged (ALK-positive) Metastatic Non-small Cell Lung Cancer (NSCLC)

A Phase I study to assess the systemic exposure, effiacy, and safety of 450 mg ceritinib taken with a low-fat meal and 600 mg ceritinib taken with a low-fat meal as compared with that of 750 mg ceritinib taken in the fasted state in adult patients with ALK rearranged (ALK-positive) metastatic non-small cell lung cancer (NSCLC)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was an open-label, randomized, multi-center, parallel design, Phase I study in which the systemic exposure, efficacy and safety of ceritinib administered at 450 mg or 600 mg with a low-fat meal vs 750 mg in the fasted state was assessed in subjects with ALK+ NSCLC following multiple oral daily dosing of ceritinib. Subjects were randomized in a 1:1:1 ratio to once daily doses of oral ceritinib (450 mg following a low-fat meal, 600 mg following a low-fat meal or ceritinib 750 mg administered on an empty stomach). Randomization was stratified by brain metastases at Screening (presence or absence) and by prior treatment (prior crizotinib use with ALK+ determined by Fluorescent in situ hybridization (FISH); crizotinib-naïve but could be previously treated with other systemic anti-cancer therapy with ALK+ determined by FISH, or treatment-naïve subjects with ALK+ by IHC).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
306

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Auckland, Australia
        • Novartis Investigative Site
    • Auckland
      • Grafton, Auckland, Australia
        • Novartis Investigative Site
  • Austria
      • Wien, Austria, 1210
        • Novartis Investigative Site
      • Wien, Austria, A-1140
        • Novartis Investigative Site
  • Belgium
      • Edegem, Belgium, 2650
        • Novartis Investigative Site
  • Brazil
    • RN
      • Natal, RN, Brazil, 59075 740
        • Novartis Investigative Site
    • RS
      • Passo Fundo, RS, Brazil, 99010-260
        • Novartis Investigative Site
      • Porto Alegre, RS, Brazil, 90601-000
        • Novartis Investigative Site
    • SC
      • Itajai, SC, Brazil, 88301-229
        • Novartis Investigative Site
    • SP
      • Barretos, SP, Brazil, 14784 400
        • Novartis Investigative Site
      • Sao Paulo, SP, Brazil, 01246 000
        • Novartis Investigative Site
  • Bulgaria
      • Sofia, Bulgaria, 1303
        • Novartis Investigative Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Novartis Investigative Site
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Novartis Investigative Site
      • Ottawa, Ontario, Canada, K1H 8L6
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • Colombia
      • Monteria, Colombia
        • Novartis Investigative Site
  • Czechia
      • Brno, Czechia, 65653
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 12351
        • Novartis Investigative Site
      • Koeln, Germany, 51109
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97074
        • Novartis Investigative Site
    • Bavaria
      • Regensburg, Bavaria, Germany, 93053
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, GR14564
        • Novartis Investigative Site
    • GR
      • Athens, GR, Greece, 115 27
        • Novartis Investigative Site
  • India
      • Delhi, India, 110 085
        • Novartis Investigative Site
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500 034
        • Novartis Investigative Site
    • Karnataka
      • Bangalore, Karnataka, India, 560 095
        • Novartis Investigative Site
    • Maharashtra
      • Nashik, Maharashtra, India, 422002
        • Novartis Investigative Site
    • West Bengal
      • Kolkata, West Bengal, India, 700063
        • Novartis Investigative Site
  • Italy
      • Novara, Italy, 28100
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italy, 24127
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • BS
      • Brescia, BS, Italy, 25123
        • Novartis Investigative Site
    • FC
      • Meldola, FC, Italy, 47014
        • Novartis Investigative Site
    • FG
      • San Giovanni Rotondo, FG, Italy, 71013
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Italy, 33081
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00155
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 06351
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 03722
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
  • Lebanon
      • Ashrafieh, Lebanon, 166484
        • Novartis Investigative Site
  • Malaysia
      • Pulau Pinang, Malaysia, 10990
        • Novartis Investigative Site
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Novartis Investigative Site
  • Netherlands
      • Nieuwegein, Netherlands, 3435 CM
        • Novartis Investigative Site
  • Poland
      • Gdansk, Poland, 80 952
        • Novartis Investigative Site
      • Konin, Poland, 62 500
        • Novartis Investigative Site
      • Tarnobrzeg, Poland, 39-400
        • Novartis Investigative Site
  • Russian Federation
      • St Petersburg, Russian Federation, 197343
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28050
        • Novartis Investigative Site
      • Madrid, Spain, 28222
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Spain, 41009
        • Novartis Investigative Site
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Novartis Investigative Site
    • Pais Vasco
      • San Sebastian, Pais Vasco, Spain, 20080
        • Novartis Investigative Site
  • Taiwan
      • Taichung, Taiwan, 40447
        • Novartis Investigative Site
      • Taipei, Taiwan, 110
        • Novartis Investigative Site
      • Taoyuan, Taiwan, 33305
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10700
        • Novartis Investigative Site
    • Songkla
      • Hat Yai, Songkla, Thailand, 90110
        • Novartis Investigative Site
    • THA
      • Bangkok, THA, Thailand, 10330
        • Novartis Investigative Site
  • Turkey
      • Talas / Kayseri, Turkey, 38039
        • Novartis Investigative Site
  • United Kingdom
    • Merseyside
      • Wirral, Merseyside, United Kingdom, CH63 4JY
        • Novartis Investigative Site
    • Newcastle
      • Newcastle Upon Tyne, Newcastle, United Kingdom, NE7 7DN
        • Novartis Investigative Site
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Goshen Center for Cancer Care IU Health - SC
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Maryland Oncology Hematology, P.A. SC-2
    • New Jersey
      • Belleville, New Jersey, United States, 07109
        • Essex Oncology of North Jersey PA SC
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • Greenville Health System SC
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate for definitive multimodality therapy) or IV ALK-positive NSCLC.
  • Patients may have received one prior treatment regimen with crizotinib (all other ALK inhibitors are excluded).
  • Patients may have received prior chemotherapy, biologic therapy, or other investigational agents. ALK inhibitors other than crizotinib are excluded.
  • Patient has a World Health Organization (WHO) performance status 0-2.

Exclusion Criteria:

  • Prior treatment with an ALK inhibitor other than crizotinib.
  • 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.
  • Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)
  • 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).
  • Patient has other severe, acute, or chronic medical conditions
  • Patient is currently receiving treatment with warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ceritinib 450 mg with a low-fat meal
Oral ceritinib QD (21 days/ cycle) at a dose of 450 mg (3×150 mg/capsule) administered in the morning immediately (within 30 minutes)following a low-fat meal.
Drug: ceritinib
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Other Names:
  • LDK378
Experimental: ceritinib 600 mg with a low-fat meal
Oral ceritinib QD (21 days/ cycle) at a dose of 600 mg (4×150 mg/capsule) administered in the morning immediately (within 30 minutes) following a low-fat meal.
Drug: ceritinib
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Other Names:
  • LDK378
Active Comparator: ceritinib 750 mg on an empty stomach
Oral ceritinib QD (21 days/ cycle) at a dose of 750 mg (5×150 mg/capsule) administered in the morning on an empty stomach (i.e., fasted from food and drink except water)
Drug: ceritinib
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Other Names:
  • LDK378

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma concentration of ceritinib
Time Frame: Study Day 22
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Study Day 22

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety profile
Time Frame: The primary analysis will be based on data from all patients, up to the time at which all randomized patients have completed at least 12 weeks of ceritinib treatment or have discontinued study treatment, whichever is earlier.
Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities
The primary analysis will be based on data from all patients, up to the time at which all randomized patients have completed at least 12 weeks of ceritinib treatment or have discontinued study treatment, whichever is earlier.
Plasma concentration of ceritinib
Time Frame: Study Day 1
PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Study Day 1
Objective response rate (ORR)
Time Frame: Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Recist v1.1; Cycle = 21 days
Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Duration of response (DOR)
Time Frame: Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Recist v1.1
Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 9, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 16, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 6, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLDK378A2112
  • 2014-004001-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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