Clinical trial NCT01685060: LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib
Official title: A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
NSCLC
ALK
LDK378
Ceritinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-09-13
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined progressive disease (PD) as assessed by the investigator if, in the judgment of the investigator, there was evidence of clinical benefit. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator


Eligibility criteria: Inclusion critieria:

* Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
* Age 18 years or older at the time of informed consent.
* Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
* Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
* Patients must have a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
* Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

Exclusion criteria:

* Patients with known hypersensitivity to any of the excipients of LDK378.
* Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
* History of carcinomatous meningitis.
* Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
* Clinically significant, uncontrolled heart disease
* Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.

Primary outcomes:
measure: Overall Response Rate (ORR) to LDK378 Per Investigator Assessment
timeFrame: 6 cycles of 28 days up to 24 weeks
Secondary outcomes:
measure: ORR Per Blinded Independent Review Committee (BIRC) Assessment
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Duration of Response (DOR) by Investigator
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Duration of Response (DOR) by BIRC
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Disease Control Rate (DCR)
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Time to Response (TTR) Per Investigator
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Time to Response (TTR) Per BIRC
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Progression-free Survival (PFS) Per Investigator
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Progression-free Survival (PFS) Per BIRC
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Overall Intracranial Response Rate (OIRR) Per Investigator
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Overall Intracranial Response Rate (OIRR) Per BIRC
timeFrame: 6 cycles of 28 days up to 24 weeks
measure: Overall Survival (OS)
timeFrame: 6 cycles of 28 days up to 24 weeks
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center Dept of Oncology 2
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles Reg-5
state: California
city: San Diego
country: United States
facility: University of California at San Diego, Moores Cancer Ctr SC
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford Cancer Center(2)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital SC
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Dept of Oncology
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center SC
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Cancer Center DeptofUofKansas CancerCenter-2
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas Dept of CCK
state: Kansas
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. SC
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General
state: Massachusetts
city: Charlotte
country: United States
facility: Levine Cancer Institute SC 1
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Drug Ship - 4
state: Tennessee
city: Dallas
country: United States
facility: U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance SC-1
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Univ Wisc 2
state: Wisconsin
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Oshawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Marseille cedex 20
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Avellino
country: Italy
facility: Novartis Investigative Site
state: AV
city: Livorno
country: Italy
facility: Novartis Investigative Site
state: LI
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Akashi
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sunto-gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
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
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hida T, Satouchi M, Nakagawa K, Seto T, Matsumoto S, Kiura K, Nokihara H, Murakami H, Tokushige K, Hatano B, Nishio M. Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset. Jpn J Clin Oncol. 2017 Jul 1;47(7):618-624. doi: 10.1093/jjco/hyx045.
citation: Crino L, Ahn MJ, De Marinis F, Groen HJ, Wakelee H, Hida T, Mok T, Spigel D, Felip E, Nishio M, Scagliotti G, Branle F, Emeremni C, Quadrigli M, Zhang J, Shaw AT. Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib: Results From ASCEND-2. J Clin Oncol. 2016 Aug 20;34(24):2866-73. doi: 10.1200/JCO.2015.65.5936. Epub 2016 Jul 18.