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)

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)

Brief Title

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).

Categories

Lung & Chest Cancers

Cancer

Lung

COVID-19

Asthma and Other Respiratory Diseases

Completion Date

2020-03-06

Completion Date Type

Actual

Conditions

Non-Small Cell Lung Cancer

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.

Inclusion 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.

Gender

All

Gender Based

false

Keywords

LDK378

ceritinib

Alk+

Alk positive

NSCLC

lung Cancer

Healthy Volunteers

No

Last Update Post Date

Wed, 02/09/2022 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Mon, 02/07/2022 - 12:00

Minimum Age

18 Years

NCT Id

NCT02299505

Org Class

Industry

Org Full Name

Novartis

Org Study Id

CLDK378A2112

Overall Status

Completed

Phases

Phase 1

Primary Completion Date

Thu, 06/16/2016 - 12:00

Primary Completion Date Type

Actual

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)

Primary Outcomes

Outcome Description

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

Outcome Measure

Plasma concentration of ceritinib

Outcome Time Frame

Study Day 22

Secondary Ids

Secondary Id

2014-004001-32

Secondary Outcomes

Outcome Description

Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities

Outcome 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.

Outcome Measure

Safety profile

Outcome Description

PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F

Outcome Time Frame

Study Day 1

Outcome Measure

Plasma concentration of ceritinib

Outcome Description

Recist v1.1; Cycle = 21 days

Outcome Time Frame

Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.

Outcome Measure

Objective response rate (ORR)

Outcome Description

Recist v1.1

Outcome Time Frame

Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.

Outcome Measure

Duration of response (DOR)