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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01828099




Registration number
NCT01828099
Ethics application status
Date submitted
3/04/2013
Date registered
10/04/2013
Date last updated
24/01/2024

Titles & IDs
Public title
LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
Scientific title
A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer
Secondary ID [1] 0 0
2013-000319-26
Secondary ID [2] 0 0
CLDK378A2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ceritinib
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin

Experimental: Ceritinib - Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state.

Active Comparator: Chemotherapy - Chemotherapy patients (Induction per Investigator's choice) were on four 21-day cycles of Pemetrexed 500mg/m2 iv + Cisplatin 75 mg/m2 or Pemetrexed 500 mg/m2 iv + Carboplatin AUC 5-6 iv followed by Pemetrexed 500 mg/m2 every 21 days followed by Pemetrexed maintenance in non-progressors, etc (other usual rule to stop treatment).


Treatment: Drugs: Ceritinib
Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.

Treatment: Drugs: Pemetrexed
Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.

Treatment: Drugs: Cisplatin
Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.

Treatment: Drugs: Carboplatin
Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)
Timepoint [1] 0 0
from the date of randomization to the date of first radiologically documented disease progression or death due to any cause (assessed every 6 weeks up to approximately 34 months)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until death (up to approximately 34 months)
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
From randomization until death (up to approximately 34 months)
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
From randomization until death (up to approximately 34 months)
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
From randomization until death (up to approximately 34 months)
Secondary outcome [5] 0 0
Time to Response (TTR)
Timepoint [5] 0 0
From randomization until death (up to approximately 34 months)
Secondary outcome [6] 0 0
Patient Reported Outcomes
Timepoint [6] 0 0
Screening, followed by every 6 weeks until Month 33 after Month 33 every 9 weeks.

Eligibility
Key inclusion criteria
1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous
Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive
as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed
at Novartis designated central laboratories.

2. Patient has newly diagnosed stage IIIB (who are not a candidate for definitive
multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic
NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic
drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other
targeted therapies, either experimental or not), with exception of neo-adjuvant or
adjuvant therapy

3. Patient has at least one measurable lesion as defined by RECIST 1.1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient with known hypersensitivity to any of the excipients of LDK378
(microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and
magnesium stearate)

2. Patient with a history of severe hypersensitivity reaction to platinum containing
drugs, pemetrexed or any known excipients of these drugs.

3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically
unstable or has required increasing doses of steroids within the 2 weeks prior to
screening to manage CNS symptoms.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/01/2024
Sample size
Target
Accrual to date
Final
376
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [3] 0 0
Novartis Investigative Site - Auckland
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
92024 - Auckland
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Salzburg
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Austria
State/province [2] 0 0
Wien
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Brazil
State/province [3] 0 0
Rio Grande Do Sul
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Brazil
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RN
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Brazil
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SC
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Brazil
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SP
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China
State/province [7] 0 0
Beijing
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China
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Chongqing
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China
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Guangdong
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China
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Jilin
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China
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Shanghai
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China
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Shanxi
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China
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Sichuan
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China
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Zhejiang
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China
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Guang Dong Province
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China
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Tianjin
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Colombia
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Monteria
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Denmark
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Herlev
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Denmark
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Odense C
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France
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Val De Marne
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France
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Caen
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France
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Grenoble
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France
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Lille Cedex
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France
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Limoges Cedex
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France
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Paris 10
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France
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Pierre Benite
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France
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Rennes
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France
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Strasbourg Cedex
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France
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Villejuif
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Germany
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Gottingen
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Germany
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Heidelberg
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Germany
State/province [32] 0 0
Tuebingen
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Germany
State/province [33] 0 0
Ulm
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Germany
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Wiesbaden
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Greece
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Heraklion Crete
Country [36] 0 0
India
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Andhra Pradesh
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India
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Karnataka
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India
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Maharashtra
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India
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Rajasthan
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India
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Tamil Nadu
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India
State/province [41] 0 0
West Bengal
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India
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Delhi
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India
State/province [43] 0 0
Mumbai
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Ireland
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Dublin 4
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Italy
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AN
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Italy
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BG
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Italy
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GE
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Italy
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MB
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Italy
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MI
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Italy
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PG
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Italy
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PI
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Italy
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PN
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Italy
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PR
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Italy
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RE
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Italy
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RM
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Italy
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TO
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Italy
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UD
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Italy
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Napoli
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Japan
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Aichi
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Japan
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Chiba
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Hyogo
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Japan
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Osaka
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Japan
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Tokyo
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Japan
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Niigata
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Korea, Republic of
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Gyeonggi Do
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Korea, Republic of
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Korea
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Korea, Republic of
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Seoul
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Ashrafieh
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Saida
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Mexico
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Jalisco
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AZ
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Netherlands
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Amsterdam
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Breda
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Groningen
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Leiden
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Oslo
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Catalunya
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Barcelona
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Madrid
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Linkoping
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Lund
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Stockholm
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Sweden
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Uppsala
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Taiwan
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Taiwan, ROC
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Taoyuan
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Kaohsiung
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Taichung City
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Taichung
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Taipei
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Thailand
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Hat Yai
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Thailand
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THA
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Thailand
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Bangkok
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Turkey
State/province [103] 0 0
Sihhiye
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Turkey
State/province [104] 0 0
Istanbul
Country [105] 0 0
United Kingdom
State/province [105] 0 0
West Yorkshire
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Birmingham
Country [107] 0 0
United Kingdom
State/province [107] 0 0
London
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United Kingdom
State/province [108] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary purpose of the study was to compare the antitumor activity of LDK378 versus
reference chemotherapy. Patients in the chemotherapy arm were given the option to switch to
LDK378 after confirmed progressive disease (PD), while also had the choice to continue with
pemetrexed treatment.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01828099
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries