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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

306

Phase

  • 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

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
Intervention / Treatment
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

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

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

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)

April 9, 2015

Primary Completion (Actual)

June 16, 2016

Study Completion (Actual)

March 6, 2020

Study Registration Dates

First Submitted

November 14, 2014

First Submitted That Met QC Criteria

November 20, 2014

First Posted (Estimate)

November 24, 2014

Study Record Updates

Last Update Posted (Actual)

February 9, 2022

Last Update Submitted That Met QC Criteria

February 7, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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