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)
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
306
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Highlands Oncology Group
Fayetteville, Arkansas, United States
Loma Linda University
Loma Linda, California, United States
Goshen Center for Cancer Care IU Health - SC
Indianapolis, Indiana, United States
Maryland Oncology Hematology, P.A. SC-2
Rockville, Maryland, United States
Essex Oncology of North Jersey PA SC
Belleville, New Jersey, United States
Plasma concentration of ceritinib
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Time frame: Study Day 22
Safety profile
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.
Plasma concentration of ceritinib
PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Time frame: Study Day 1
Objective response rate (ORR)
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.
Duration of response (DOR)
Recist v1.1
Time frame: Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
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Greenville Health System SC
Greenville, South Carolina, United States
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, United States
Novartis Investigative Site
Grafton, Auckland, Australia
Novartis Investigative Site
Auckland, Australia
Novartis Investigative Site
Vienna, Austria
...and 63 more locations