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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/NCT02737501




Registration number
NCT02737501
Ethics application status
Date submitted
30/03/2016
Date registered
14/04/2016
Date last updated
20/08/2021

Titles & IDs
Public title
ALTA-1L Study: A 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: Randomized Phase: Brigatinib 90 mg QD/180 QD - Brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, orally, QD, in each 28-day cycle until PD, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 34.86 months).

Active Comparator: Randomized Phase: Crizotinib 250 mg BID - Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months).

Experimental: Crossover Phase: Brigatinib 90 mg QD/180 mg QD - Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months).


Treatment: Drugs: Brigatinib
Brigatinib tablets

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Up to end of study (Up to 56 months)
Secondary outcome [1] 0 0
Confirmed Objective Response Rate (ORR)
Timepoint [1] 0 0
Baseline up to end of treatment (Up to 36 months)
Secondary outcome [2] 0 0
Confirmed Intracranial ORR (iORR)
Timepoint [2] 0 0
Baseline up to end of treatment (Up to 36 months)
Secondary outcome [3] 0 0
Intracranial Progression Free Survival
Timepoint [3] 0 0
Baseline up to end of study (Up to 56 months)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Baseline up to end of study (Up to 56 months)
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
Baseline up to end of study (Up to 56 months)
Secondary outcome [6] 0 0
Time to Response (TTR)
Timepoint [6] 0 0
Baseline up to end of treatment (Up to 36 months)
Secondary outcome [7] 0 0
Disease Control Rate (DCR)
Timepoint [7] 0 0
Baseline up to end of treatment (Up to 36 months)
Secondary outcome [8] 0 0
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [8] 0 0
From first dose up to 30 days after last dose of study drug (Up to approximately 37 months)
Secondary outcome [9] 0 0
Change From Baseline in Global Health Status/Quality of Life as Assessed by EORTC QLQ-C30 (Version 3.0)
Timepoint [9] 0 0
Baseline and Month 36

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
Sex
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
26/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/01/2021
Sample size
Target
Accrual to date
Final
275
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 - Bentleigh East
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 - Bentleigh East
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
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
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
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Denmark
State/province [15] 0 0
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
Country [20] 0 0
France
State/province [20] 0 0
Rhone-alpes
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-wuerttemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Niedersachsen
Country [23] 0 0
Germany
State/province [23] 0 0
Nordrhein-westfalen
Country [24] 0 0
Germany
State/province [24] 0 0
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
State/province [29] 0 0
Forli-cesena
Country [30] 0 0
Italy
State/province [30] 0 0
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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Barcelona
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Madrid
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Alicante
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Spain
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La Coruna
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Malaga
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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
State/province [62] 0 0
Taipei
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Taiwan
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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/ct2/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