LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer
A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer
2 other identifiers
interventional
124
18 countries
51
Brief Summary
A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was 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. 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. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started Dec 2012
Typical duration for phase_2 nonsmall-cell-lung-cancer
51 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 4, 2012
CompletedFirst Posted
Study publicly available on registry
September 14, 2012
CompletedStudy Start
First participant enrolled
December 20, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 22, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 22, 2018
CompletedResults Posted
Study results publicly available
February 12, 2019
CompletedMarch 26, 2019
March 1, 2019
5.1 years
September 4, 2012
January 22, 2019
March 12, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) by Investigator Assessment
ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by the investigator. CR:Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary Outcomes (10)
ORR by Blinded Independent Review Committee (BIRC)
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Duration of Response (DOR) as Per Investigator
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Duration of Response (DOR) as Per BIRC
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Disease Control Rate (DCR) as Per Investigator and BIRC
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Time to Response (TTR) as Per Investigator
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug
- +5 more secondary outcomes
Study Arms (1)
LDK378 (Ceritinib)
EXPERIMENTALParticipants on this arm took oral LDK378 750 mg once daily.
Interventions
LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carried an ALK rearrangement, as per the FDA-approved Vysis ALK break-apart FISH assay (Abbott Molecular Inc.)
- Age 18 years or older at the time of informed consent.
- Patients must have NSCLC that had progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was received
- Patients must have been chemotherapy-naive or had received 1-3 lines of cytotoxic chemotherapy to treat their locally advanced or metastatic NSCLC
- Patients must have had 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 were not allowed to participate in the study.
You may not qualify if:
- Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC
- Patients with known hypersensitivity to any of the excipients of LDK378.
- Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
Massachusetts General Hospital Mass Gen 5
Boston, Massachusetts, 02114, United States
Washington University School of Medicine Washington University (16)
St Louis, Missouri, 63110, United States
Sarah Cannon Research Institute Drug Ship - 4
Nashville, Tennessee, 37203, United States
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
Dallas, Texas, 75390, United States
Novartis Investigative Site
St Leonards, New South Wales, 2065, Australia
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Franston, Victoria, 3199, Australia
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Genk, 3600, Belgium
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Leuven, 3000, Belgium
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Toronto, Ontario, M5G 2M9, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Saint-Herblain, 44805, France
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Hong Kong, Hong Kong
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Avellino, AV, 83100, Italy
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Genova, GE, 16132, Italy
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Milan, MI, 20141, Italy
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Rozzano, MI, 20089, Italy
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Orbassano, TO, 10043, Italy
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Nagoya, Aichi-ken, 464 8681, Japan
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Kashiwa, Chiba, 277 8577, Japan
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Fukuoka, Fukuoka, 811-1395, Japan
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Akashi, Hyōgo, 673-8558, Japan
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Sayama, Osaka, 589 8511, Japan
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Sunto Gun, Shizuoka, 411 8777, Japan
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Chuo-ku, Tokyo, 104-0045, Japan
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Koto Ku, Tokyo, 135 8550, Japan
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Auckland, 1142, New Zealand
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Oslo, NO-0424, Norway
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Chelyabinsk, 454087, Russia
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Moscow, 115478, Russia
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Saint Petersburg, 197022, Russia
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Singapore, 169610, Singapore
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Seoul, Gyeonggi-do, 03080, South Korea
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Seoul, Korea, 05505, South Korea
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Seoul, Korea, 06351, South Korea
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Seoul, 03722, South Korea
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Málaga, Andalusia, 29010, Spain
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Badalona, Catalonia, 08916, Spain
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Barcelona, Catalonia, 08035, Spain
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Madrid, 28046, Spain
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Madrid, 28050, Spain
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Stockholm, SE 171 76, Sweden
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Tainan, Taiwan ROC, 70403, Taiwan
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Taipei, Taiwan, ROC, 11217, Taiwan
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Taichung, 407, Taiwan
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Taipei, 10002, Taiwan
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Songkhla, Hat Yai, 90110, Thailand
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Colchester, CO3 3NB, United Kingdom
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London, SE1 9RT, United Kingdom
Related Publications (2)
Nishio M, Felip E, Orlov S, Park K, Yu CJ, Tsai CM, Cobo M, McKeage M, Su WC, Mok T, Scagliotti GV, Spigel DR, Viraswami-Appanna K, Chen Z, Passos VQ, Shaw AT. Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC. J Thorac Oncol. 2020 Apr;15(4):609-617. doi: 10.1016/j.jtho.2019.11.006. Epub 2019 Nov 25.
PMID: 31778798DERIVEDLin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.
PMID: 27130468DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 4, 2012
First Posted
September 14, 2012
Study Start
December 20, 2012
Primary Completion
January 22, 2018
Study Completion
January 22, 2018
Last Updated
March 26, 2019
Results First Posted
February 12, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will share
- Access Criteria
- Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.