Clinical trial NCT02299505: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: LDK378
ceritinib
Alk+
Alk positive
NSCLC
lung Cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-11-24
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Plasma concentration of ceritinib
timeFrame: Study Day 22
Secondary outcomes:
measure: Safety profile
timeFrame: 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.
measure: Plasma concentration of ceritinib
timeFrame: Study Day 1
measure: Objective response rate (ORR)
timeFrame: Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
measure: Duration of response (DOR)
timeFrame: Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Indianapolis
country: United States
facility: Goshen Center for Cancer Care IU Health - SC
state: Indiana
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. SC-2
state: Maryland
city: Belleville
country: United States
facility: Essex Oncology of North Jersey PA SC
state: New Jersey
city: Greenville
country: United States
facility: Greenville Health System SC
state: South Carolina
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
state: Utah
city: Grafton
country: Australia
facility: Novartis Investigative Site
state: Auckland
city: Auckland
country: Australia
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Natal
country: Brazil
facility: Novartis Investigative Site
state: RN
city: Passo Fundo
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Itajai
country: Brazil
facility: Novartis Investigative Site
state: SC
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Monteria
country: Colombia
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Delhi
country: India
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: San Giovanni Rotondo
country: Italy
facility: Novartis Investigative Site
state: FG
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Novara
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Nieuwegein
country: Netherlands
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Konin
country: Poland
facility: Novartis Investigative Site
city: Tarnobrzeg
country: Poland
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Hat Yai
country: Thailand
facility: Novartis Investigative Site
state: Songkla
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Talas / Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Wirral
country: United Kingdom
facility: Novartis Investigative Site
state: Merseyside
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: