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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)

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ClinicalTrials.gov Identifier: NCT02299505
Recruitment Status : Completed
First Posted : November 24, 2014
Last Update Posted : August 25, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: ceritinib Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 306 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : April 9, 2015
Actual Primary Completion Date : June 16, 2016
Actual Study Completion Date : March 6, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ceritinib

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 Name: 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 Name: 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 Name: LDK378




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02299505


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02299505    
Other Study ID Numbers: CLDK378A2112
2014-004001-32 ( EudraCT Number )
First Posted: November 24, 2014    Key Record Dates
Last Update Posted: August 25, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LDK378
ceritinib
Alk+
Alk positive
NSCLC
lung Cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Ceritinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action