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)

Novartis

Status and phase: Completed; Phase 1

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: ceritinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02299505

2014-004001-32 (EudraCT Number)

CLDK378A2112

Details and patient eligibility

About

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)

Full 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).

Enrollment: 306 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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306 participants in 3 patient groups

ceritinib 450 mg with a low-fat meal

Experimental group

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.

Treatment:

Drug: ceritinib

ceritinib 600 mg with a low-fat meal

Experimental group

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.

Treatment:

Drug: ceritinib

ceritinib 750 mg on an empty stomach

Active Comparator group

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)

Treatment:

Drug: ceritinib