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)

Non-Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02299505
• Other study ID #: CLDK378A2112
• Secondary ID: 2014-004001-32
• Status: Completed
• Phase: Phase 1
• Start date: April 9, 2015
• Est. completion date: March 6, 2020

Study information

• Verified date: February 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: March 6, 2020
• Est. primary completion date: June 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• ceritinib
The investigational drug ceritinib was supplied to the Investigators as 150 mg capsules, for oral administration.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Auckland
Australia	Novartis Investigative Site	Grafton	Auckland
Austria	Novartis Investigative Site	Wien
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Edegem
Brazil	Novartis Investigative Site	Barretos	SP
Brazil	Novartis Investigative Site	Itajai	SC
Brazil	Novartis Investigative Site	Natal	RN
Brazil	Novartis Investigative Site	Passo Fundo	RS
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Colombia	Novartis Investigative Site	Monteria
Czechia	Novartis Investigative Site	Brno
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Delhi
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Nashik	Maharashtra
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Meldola	FC
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Novara
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	San Giovanni Rotondo	FG
Italy	Novartis Investigative Site	Verona	VR
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Pulau Pinang
Netherlands	Novartis Investigative Site	Nieuwegein
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Konin
Poland	Novartis Investigative Site	Tarnobrzeg
Russian Federation	Novartis Investigative Site	St Petersburg
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Sevilla	Andalucia
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok	THA
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Hat Yai	Songkla
Turkey	Novartis Investigative Site	Talas / Kayseri
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne	Newcastle
United Kingdom	Novartis Investigative Site	Wirral	Merseyside
United States	Essex Oncology of North Jersey PA SC	Belleville	New Jersey
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Greenville Health System SC	Greenville	South Carolina
United States	Goshen Center for Cancer Care IU Health - SC	Indianapolis	Indiana
United States	Loma Linda University	Loma Linda	California
United States	Maryland Oncology Hematology, P.A. SC-2	Rockville	Maryland
United States	Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  Germany,  Greece,  India,  Italy,  Korea, Republic of,  Lebanon,  Malaysia,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration of ceritinib	Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F	Study Day 22
Secondary	Safety profile	Gastrointestinal (GI) Adverse Events (AEs), all Serious Advers Events (AEs), vital signs, electrocardiograms (ECGs) and laboratory abnormalities	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.
Secondary	Plasma concentration of ceritinib	PK parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F	Study Day 1
Secondary	Objective response rate (ORR)	Recist v1.1; Cycle = 21 days	Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Secondary	Duration of response (DOR)	Recist v1.1	Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.

External Links

•   Results for CLDK378A2112 can be found on the Novartis Clinical Trial Results Website