Clinical trial NCT02737501: ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
Official title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lung Cancer
Advanced Malignancies
Carcinoma
Keywords: Non-small cell lung cancer
Non-small cell lung carcinoma
Epithelial lung cancer
Squamous cell carcinoma
Large cell carcinoma
Adenocarcinoma
Carcinoma
Anaplastic Lymphoma Kinase (ALK)
Advanced Cancers
Brigatinib
AP26113
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: The purpose of this phase III, randomized, open-label, comparative, multicenter, international study is to compare the efficacy and safety of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic NSCLC participants who have not previously been treated with an ALK inhibitor. Participants will be stratified by the presence of CNS metastases at baseline and prior chemotherapy used for locally advanced or metastatic disease. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 mg orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib, 250 mg orally twice daily (BID). Participants will receive treatment until disease progression, intolerable toxicity, consent withdrawal, or death. Crossover from crizotinib to brigatinib is also permitted.

The total estimated duration of the study is at least 4.5 years, including 1.5 years to accrue participants, with at least 3 years for treatment and follow-up.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to end of study (Up to 56 months)
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR)
timeFrame: Baseline up to end of treatment (Up to 36 months)
measure: Confirmed Intracranial ORR (iORR)
timeFrame: Baseline up to end of treatment (Up to 36 months)
measure: Intracranial Progression Free Survival
timeFrame: Baseline up to end of study (Up to 56 months)
measure: Overall Survival (OS)
timeFrame: Baseline up to end of study (Up to 56 months)
measure: Duration of Response (DOR)
timeFrame: Baseline up to end of study (Up to 56 months)
measure: Time to Response (TTR)
timeFrame: Baseline up to end of treatment (Up to 36 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to end of treatment (Up to 36 months)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 30 days after last dose of study drug (Up to approximately 37 months)
measure: Change From Baseline in Global Health Status/Quality of Life as Assessed by EORTC QLQ-C30 (Version 3.0)
timeFrame: Baseline and Month 36
Other outcomes:
Locations:
city: Sedona
country: United States
facility: USOR - Arizona Oncology Associates - Sedona
state: Arizona
city: Bellflower
country: United States
facility: Kaiser Permanente Bellflower Medical Offices
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers - Boulder
state: Colorado
city: Deerfield Beach
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Coon Rapids
country: United States
facility: Minnesota Oncology
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care - Blue Ash
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Kogarah
country: Australia
facility: Saint George Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Bentleigh East
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: Saint Vincent's Hospital Melbourne
state: Victoria
city: Sankt Polten
country: Austria
facility: Universitatsklinium St. Polten
state: Lower Austria
city: Vienna
country: Austria
facility: Otto-Wagner-Spital Baumgartner Hohe
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Odense C
country: Denmark
facility: Odense University Hospital
city: CAEN Cedex 5
country: France
facility: Centre de Lutte Contre le Cancer Francois Baclesse
state: Basse-normandie
city: Rouen
country: France
facility: Hopital Charles Nicolle
state: Haute-normandie
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
state: Ile-de-france
city: Paris
country: France
facility: Hopital Tenon
state: Ile-de-france
city: Marseille Cedex 20
country: France
facility: Centre Hospitalier Universitaire Hopital Nord
state: Provence Alpes COTE D'azur
city: Grenoble Cedex 9
country: France
facility: Hopital Albert Michallon
state: Rhone-alpes
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone-alpes
city: Freiburg
country: Germany
facility: Universitatsklinik Freiburg
state: Baden-wuerttemberg
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
state: Baden-wuerttemberg
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Koln
country: Germany
facility: Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim
state: Nordrhein-westfalen
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Hamburg
country: Germany
facility: Studiengesellschaft Haemato-Onkologie Hamburg Prof. Laack und Partner
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
state: New Territories
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Kowloon
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli-cesena
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Monza E Brianza
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico di Aviano
state: Pordenone
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
city: Bari
country: Italy
facility: Istituto Oncologico di Bari Giovanni Paolo II
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
city: Milano
country: Italy
facility: Istituto Scientifico Universitario San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Tumori Napoli Fondazione G. Pascale
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carita
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale di Ravenna
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg - Hopital Municipal
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis - Locatie Langendijk Breda
state: Noord-brabant
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekziekenhuis
state: Noord-holland
city: Zwolle
country: Netherlands
facility: Isala Klinieken
state: Overijssel
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Oslo
country: Norway
facility: Radiumhospitalet
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: OncoCare Cancer Centre
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: La Coruna
country: Spain
facility: Hospital Teresa Herrera - Materno Infantil
city: Madrid
country: Spain
facility: Hospital Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya Malaga Instituto de Neurociencias Clinicas
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Tainan
country: Taiwan
facility: National Cheng Kung University
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: University College London
state: England
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol. 2020 Nov 1;38(31):3592-3603. doi: 10.1200/JCO.20.00505. Epub 2020 Aug 11.
citation: Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. doi: 10.1056/NEJMoa1810171. Epub 2018 Sep 25.
citation: Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. No abstract available.