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)
Completed
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| ceritinib | LDK378 | ceritinib 450 mg with a low-fat meal |
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).
| Name | Type | Description | Interventions |
|---|---|---|---|
| ceritinib 450 mg with a low-fat meal | Experimental | 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. |
|
| ceritinib 600 mg with a low-fat meal | Experimental | 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. |
|
| ceritinib 750 mg on an empty stomach | Active Comparator | 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) |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Plasma concentration of ceritinib |
| Time Frame: | Study Day 22 |
| Safety Issue: | |
| Description: | Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F |
| Measure: | 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. |
| Safety Issue: | |
| Description: | Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities |
| Measure: | Plasma concentration of ceritinib |
| Time Frame: | Study Day 1 |
| Safety Issue: | |
| Description: | PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F |
| Measure: | Objective response rate (ORR) |
| Time Frame: | Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease. |
| Safety Issue: | |
| Description: | Recist v1.1; Cycle = 21 days |
| Measure: | Duration of response (DOR) |
| Time Frame: | Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease. |
| Safety Issue: | |
| Description: | Recist v1.1 |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
August 25, 2021
