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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)

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ceritinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring LDK378, ceritinib, Alk+, Alk positive, NSCLC, lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Highlands Oncology Group
  • Loma Linda University
  • Goshen Center for Cancer Care IU Health - SC
  • Maryland Oncology Hematology, P.A. SC-2
  • Essex Oncology of North Jersey PA SC
  • Greenville Health System SC
  • Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

ceritinib 450 mg with a low-fat meal

ceritinib 600 mg with a low-fat meal

ceritinib 750 mg on an empty stomach

Arm Description

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.

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.

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)

Outcomes

Primary Outcome Measures

Plasma concentration of ceritinib
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F

Secondary Outcome Measures

Safety profile
Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities
Plasma concentration of ceritinib
PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Objective response rate (ORR)
Recist v1.1; Cycle = 21 days
Duration of response (DOR)
Recist v1.1

Full Information

First Posted
November 14, 2014
Last Updated
February 7, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02299505
Brief Title
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)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
April 9, 2015 (Actual)
Primary Completion Date
June 16, 2016 (Actual)
Study Completion Date
March 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
LDK378, ceritinib, Alk+, Alk positive, NSCLC, lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
306 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ceritinib 450 mg with a low-fat meal
Arm Type
Experimental
Arm Description
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.
Arm Title
ceritinib 600 mg with a low-fat meal
Arm Type
Experimental
Arm Description
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.
Arm Title
ceritinib 750 mg on an empty stomach
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
ceritinib
Other Intervention Name(s)
LDK378
Intervention Description
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Primary Outcome Measure Information:
Title
Plasma concentration of ceritinib
Description
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Time Frame
Study Day 22
Secondary Outcome Measure Information:
Title
Safety profile
Description
Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities
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.
Title
Plasma concentration of ceritinib
Description
PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Time Frame
Study Day 1
Title
Objective response rate (ORR)
Description
Recist v1.1; Cycle = 21 days
Time Frame
Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Title
Duration of response (DOR)
Description
Recist v1.1
Time Frame
Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Highlands Oncology Group
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Loma Linda University
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Goshen Center for Cancer Care IU Health - SC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Maryland Oncology Hematology, P.A. SC-2
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Essex Oncology of North Jersey PA SC
City
Belleville
State/Province
New Jersey
ZIP/Postal Code
07109
Country
United States
Facility Name
Greenville Health System SC
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Novartis Investigative Site
City
Grafton
State/Province
Auckland
Country
Australia
Facility Name
Novartis Investigative Site
City
Auckland
Country
Australia
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
1210
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
A-1140
Country
Austria
Facility Name
Novartis Investigative Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Natal
State/Province
RN
ZIP/Postal Code
59075 740
Country
Brazil
Facility Name
Novartis Investigative Site
City
Passo Fundo
State/Province
RS
ZIP/Postal Code
99010-260
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90601-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Itajai
State/Province
SC
ZIP/Postal Code
88301-229
Country
Brazil
Facility Name
Novartis Investigative Site
City
Barretos
State/Province
SP
ZIP/Postal Code
14784 400
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01246 000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sofia
ZIP/Postal Code
1303
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Novartis Investigative Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Novartis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Monteria
Country
Colombia
Facility Name
Novartis Investigative Site
City
Brno
ZIP/Postal Code
65653
Country
Czechia
Facility Name
Novartis Investigative Site
City
Regensburg
State/Province
Bavaria
ZIP/Postal Code
93053
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97074
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
GR14564
Country
Greece
Facility Name
Novartis Investigative Site
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500 034
Country
India
Facility Name
Novartis Investigative Site
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560 095
Country
India
Facility Name
Novartis Investigative Site
City
Nashik
State/Province
Maharashtra
ZIP/Postal Code
422002
Country
India
Facility Name
Novartis Investigative Site
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700063
Country
India
Facility Name
Novartis Investigative Site
City
Delhi
ZIP/Postal Code
110 085
Country
India
Facility Name
Novartis Investigative Site
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Novartis Investigative Site
City
San Giovanni Rotondo
State/Province
FG
ZIP/Postal Code
71013
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Aviano
State/Province
PN
ZIP/Postal Code
33081
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00155
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Ashrafieh
ZIP/Postal Code
166484
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Gdansk
ZIP/Postal Code
80 952
Country
Poland
Facility Name
Novartis Investigative Site
City
Konin
ZIP/Postal Code
62 500
Country
Poland
Facility Name
Novartis Investigative Site
City
Tarnobrzeg
ZIP/Postal Code
39-400
Country
Poland
Facility Name
Novartis Investigative Site
City
St Petersburg
ZIP/Postal Code
197343
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41009
Country
Spain
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Novartis Investigative Site
City
San Sebastian
State/Province
Pais Vasco
ZIP/Postal Code
20080
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
110
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taoyuan
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Hat Yai
State/Province
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
State/Province
THA
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Talas / Kayseri
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Novartis Investigative Site
City
Wirral
State/Province
Merseyside
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle Upon Tyne
State/Province
Newcastle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17802
Description
Results for CLDK378A2112 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

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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