Non-Small Cell Lung Cancer
Conditions
Keywords
LDK378, ceritinib, Alk+, Alk positive, NSCLC, lung Cancer
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).
Interventions
DRUGceritinib
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of ceritinib | Study Day 22 | Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile | 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 |
| Plasma concentration of ceritinib | Study Day 1 | PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F |
| Objective response rate (ORR) | Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease. | Recist v1.1; Cycle = 21 days |
| Duration of response (DOR) | Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease. | Recist v1.1 |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Czechia, Germany, Greece, India, Italy, Lebanon, Malaysia, Netherlands, Poland, Russia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed