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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02737501




Registration number
NCT02737501
Ethics application status
Date submitted
30/03/2016
Date registered
14/04/2016
Date last updated
23/12/2020

Titles & IDs
Public title
ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
Scientific title
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
Secondary ID [1] 0 0
U1111-1210-4363
Secondary ID [2] 0 0
AP26113-13-301
Universal Trial Number (UTN)
Trial acronym
ALTA-1L
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Lung Cancer 0 0
Advanced Malignancies 0 0
Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
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 - Brigatinib
Treatment: Drugs - Crizotinib

Experimental: Brigatinib - Brigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 milligram (mg) QD for 7 days, then 180 mg QD, continuously, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.

Active Comparator: Crizotinib - Crizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.


Treatment: Drugs: Brigatinib
Brigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, until disease progression, unacceptable toxicity, withdrawal of consent or death.

Treatment: Drugs: Crizotinib
Crizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, until disease progression, unacceptable toxicity, withdrawal of consent or death.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) - PFS as assessed by blinded Independent Review Committee (BIRC) is defined as the time interval from the date of randomization until the first date at which disease progression (PD) is objectively documented, or death due to any cause, whichever occurs first. PD is sum of longest diameter (SLD) increased by at least 20 percent (%) from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 millimeter (mm), and unequivocal progression of existing non-target lesions.
Timepoint [1] 0 0
Baseline up to approximately 36 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) - ORR as assessed by BIRC, is defined as percentage of participants who are confirmed to have achieved complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1 criteria. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to less than (<) 10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Timepoint [1] 0 0
Baseline up to approximately 36 months
Secondary outcome [2] 0 0
Intracranial ORR - Intracranial ORR as assessed by BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) in randomized participants with intracranial CNS metastasis at baseline. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Timepoint [2] 0 0
Baseline up to approximately 36 months
Secondary outcome [3] 0 0
Intracranial PFS - Intracranial PFS as assessed by BIRC, is defined as the time from randomization until first CNS PD is documented, or death due to any cause. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Timepoint [3] 0 0
Baseline up to approximately 36 months
Secondary outcome [4] 0 0
Overall Survival (OS) - Overall survival is defined as the time from randomization until death due to any cause.
Timepoint [4] 0 0
Baseline up to approximately 36 months
Secondary outcome [5] 0 0
Duration of Response - Duration of response as assessed by BIRC, is defined as the time interval from the date that the criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30 % decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and for non-target lesions, unequivocal progression of existing non-target lesions.
Timepoint [5] 0 0
Baseline up to approximately 36 months
Secondary outcome [6] 0 0
Time to Response (TTR) - Time to response as assessed by BIRC, assessment and is defined as the time interval from the date randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.
Timepoint [6] 0 0
Baseline up to approximately 36 months
Secondary outcome [7] 0 0
Disease Control Rate (DCR) - Disease control as assessed by BIRC, defined as percentage of randomized participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, criteria for SD must have been met at least once after randomization at a minimum interval of 6 weeks) after randomization. CR defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: SLD increased by at least 20% from the smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Timepoint [7] 0 0
Baseline up to approximately 36 months
Secondary outcome [8] 0 0
Health-related Quality of Life (HRQoL) - HRQoL is defined as the perceived quality of the participant's life, which includes self-reported multidimensional measures of physical and mental health. Patient-reported symptoms (PROs) and HRQoL will be collected by administering the european organisation for research and treatment of cancer (EORTC) quality of life (QLQ)-C30 questionnaire. EORTC-QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. The 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For functional scales and QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Timepoint [8] 0 0
Baseline until 30 days after the last dose of study treatment (approximately 3 years)
Secondary outcome [9] 0 0
Percentage of Participants with Adverse Events
Timepoint [9] 0 0
Baseline until 30 days after the last dose of study treatment (approximately 3 years)

Eligibility
Key inclusion criteria
1. Have histologically or cytologically confirmed stage IIIB (and not a candidate for
definitive multimodality therapy) or stage four (IV) NSCLC.

2. Must have documented ALK rearrangement.

3. Have sufficient tumor tissue available for central analysis.

4. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.

5. Recovered from toxicities related to prior anticancer therapy to National Cancer
Institute (of the United States) (NCI) Common Terminology Criteria for Adverse Events
(version 4.0) (CTCAE v 4.0) grade be less than or equal to (<=) 1.

6. Are a male or female participants greater than or equal to (>=)18 years old.

7. Have adequate organ function, as defined by the study protocol.

8. Have Eastern Cooperative Oncology Group (ECOG) performance status <=2.

9. Have normal QT interval on screening ECG evaluation, defined as QT interval corrected
(Fridericia) (QTcF) of <= 450 millisecond (msec) in males or <=470 msec in females.

10. For female participants of childbearing potential, have a negative pregnancy test
documented prior to randomization.

11. For female and male participants who are fertile, agree to use a highly effective form
of contraception, as defined by the study protocol.

12. Provide signed and dated informed consent indicating that the participants has been
informed of all pertinent aspects of the study, including the potential risks, and is
willingly participating.

13. Have the willingness and ability to comply with scheduled visit and study procedures.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previously received an investigational antineoplastic agent for NSCLC.

2. Previously received any prior tyrosine kinase inhibitor (TKI), including ALK-targeted
TKIs.

3. Previously received more than 1 regimen of systemic anticancer therapy for locally
advanced or metastatic disease.

4. Received chemotherapy or radiation within 14 days of first dose of study drug, except
stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).

5. Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of
study drug.

6. Had major surgery within 30 days of the first dose of study drug, minor surgical
procedures such as catheter placement or minimally invasive biopsies are allowed.

7. Have been diagnosed with another primary malignancy other than NSCLC, except for
adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively
treated non-metastatic prostate cancer; or participants with another primary
malignancy who are definitively relapse-free with at least 3 years elapsed since the
diagnosis of the other primary malignancy.

8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or
asymptomatic disease requiring an increasing dose of corticosteroids to control
symptoms within 7 days prior to randomization.

9. Have current spinal cord compression (symptomatic or asymptomatic and detected by
radiographic imaging). Participants with leptomeningeal disease and without cord
compression are allowed.

10. Be pregnant, planning a pregnancy, or breastfeeding.

11. Have significant, uncontrolled, or active cardiovascular disease, as defined by the
study protocol.

12. Have uncontrolled hypertension.

13. Have a history or the presence at baseline of pulmonary interstitial disease,
drug-related pneumonitis, or radiation pneumonitis.

14. Have an ongoing or active infection.

15. Have a known history of human immunodeficiency virus (HIV) infection.

16. Have a known or suspected hypersensitivity to brigatinib or its excipients and/or
crizotinib or its excipients.

17. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.

18. Have any condition or illness that, in the opinion of the investigator, would
compromise participant's safety or interfere with the evaluation of the study drug.

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Saint George Hospital - Kogarah
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Monash Medical Centre - East Bentleigh
Recruitment hospital [4] 0 0
Saint Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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United States of America
State/province [4] 0 0
Florida
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Austria
State/province [12] 0 0
Lower Austria
Country [13] 0 0
Austria
State/province [13] 0 0
Vienna
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Canada
State/province [14] 0 0
Ontario
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Denmark
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Odense C
Country [16] 0 0
France
State/province [16] 0 0
Basse-normandie
Country [17] 0 0
France
State/province [17] 0 0
Haute-normandie
Country [18] 0 0
France
State/province [18] 0 0
Ile-de-france
Country [19] 0 0
France
State/province [19] 0 0
Provence Alpes COTE D'azur
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France
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Rhone-alpes
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Germany
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Baden-wuerttemberg
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Germany
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Niedersachsen
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Germany
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Nordrhein-westfalen
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Germany
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Berlin
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Germany
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Hamburg
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Hong Kong
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New Territories
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Hong Kong
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Hong Kong
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Hong Kong
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Kowloon
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Italy
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Forli-cesena
Country [30] 0 0
Italy
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Monza E Brianza
Country [31] 0 0
Italy
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Pordenone
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Italy
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Avellino
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Italy
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Bari
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Italy
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Bologna
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Italy
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Milano
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Italy
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Napoli
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Italy
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Novara
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Italy
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Perugia
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Italy
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Ravenna
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Italy
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Roma
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Korea, Republic of
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Chungcheongbuk-do
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seoul
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Luxembourg
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Luxembourg
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Netherlands
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Noord-brabant
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Netherlands
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Noord-holland
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Netherlands
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Overijssel
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Netherlands
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Groningen
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Norway
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Oslo
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Singapore
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Singapore
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Alicante
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Spain
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La Coruna
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Spain
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Malaga
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Spain
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Santander
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Spain
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Sevilla
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Spain
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Valencia
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Sweden
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Stockholm
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Switzerland
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Zurich
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Taiwan
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Taipei
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Taiwan
State/province [63] 0 0
Taichung
Country [64] 0 0
United Kingdom
State/province [64] 0 0
England

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to compare the efficacy of brigatinib to that of crizotinib in
ALK+ locally advanced or metastatic non-small cell lung cancer (NSCLC) participants naive to
ALK inhibitors, as evidenced by progression-free survival (PFS).
Trial website
https://clinicaltrials.gov/show/NCT02737501
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Takeda
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

Summary results
Other publications