A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants (ALEX)

Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer

This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. The study is expected to last approximately 144 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Alectinib; Drug: Crizotinib

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria, Australia, 3168
    • Monash Health Translational Precinct; Clinical Trials Centre, Level 3
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre; St Vincents Hospital
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Oncology
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle; Medical Oncology
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Queen Elizabeth Hospital; Medical Oncology
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska; Clinic for Pulmonary Diseases
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinical Center Sarajevo;Clinic for Pulmonary disease
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinical Center Sarajevo;Institute of oncology
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital; Oncology
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre; Uni of Saskatoon Campus
• Chile
  • Santiago, Chile, 8420383
    • Centro Internacional de Estudios Clínicos (CIEC)
• China
  • Guangzhou City, China, 510663
    • Sun Yet-sen University Cancer Center
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
• Egypt
  • Cairo, Egypt, 11555
    • Kasr Eieny Uni Hospital; Oncology (Nemrock)
• France
  • Grenoble, France, 38043
    • Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie
  • Lille, France, 59037
    • CHRU de Lille
  • Lyon, France, 69373
    • Centre Leon Berard; Departement Oncologie Medicale
  • Pessac, France, 33600
    • Hôpital Haut Lévêque
  • Rennes, France, 35033
    • Hôpital Pontchaillou
• Germany
  • Karlsruhe, Germany, 76137
    • St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie
  • Löwenstein, Germany, 74245
    • Klinik Löwenstein gGmbH Medizinische Klinik II
• Guatemala
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles
• Hong Kong
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital; Oncology
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital; Clinical Oncology
  • Hong Kong, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital; Clinical Oncology
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Medicine & Respiratory
  • Shatin, Hong Kong
    • Prince of Wales Hosp; Dept. Of Clinical Onc
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center; Oncology
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center; Oncology
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Seconda Universita' Degli Studi; Divsione Di Oncologia Medica
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • A.O. Universitaria Di Parma; Oncologia Medica
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
  • Sicilia
    • Catania, Sicilia, Italy, 95122
      • Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
  • Umbria
    • Sant'Andrea Delle Fratte (PG), Umbria, Italy, 06132
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Mexico
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 14080
      • Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación
• New Zealand
  • Auckland, New Zealand
    • Uni of Auckland; Medical School
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
  • Lublin, Poland, 20-064
    • Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej
  • Olsztyn, Poland, 10-357
    • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii
  • Otwock, Poland, 05-400
    • Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
• Portugal
  • Coimbra, Portugal, 3000-075
    • CHUC - Unidade de Pneumologia Oncológica; Hospital de Dia de Oncologia Edificio Sao Jeronimo
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa; Servico de Pneumologia
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Russian Federation
  • Novosibirsk, Russian Federation, 630047
    • City Clinical Hospital No. 1
  • Kaluga
    • Obninsk, Kaluga, Russian Federation, 249036
      • Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moskovskaja Oblast, Russian Federation, 105229
      • N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 197022
      • SPb City Clin Onc Dsp; Chemotherapy
    • St. Petersburg, Sankt Petersburg, Russian Federation, 197758
      • Scientific Research Oncology Institute named after N.N. Petrov; Oncology
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Sremska Kamenica, Serbia, 21204
    • Institute For Pulmonary Diseases of Vojvodina
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital; National University Cancer Institute, Singapore (NCIS)
  • Singapore, Singapore, 168583
    • National Cancer Centre; Medical Oncology
• Spain
  • Alicante, Spain, 3010
    • Hospital General Univ. de Alicante; Servicio de Oncologia
  • Barcelona, Spain, 08028
    • Hospital Universitario Quiron Dexeus
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
    • Sant Andreu de La Barca, Barcelona, Spain, 08740
      • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro; Servicio de Oncologia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel; Onkologie
  • Bern, Switzerland, 3010
    • Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit
  • Lausanne, Switzerland, 1011
    • CHUV; Departement d'Oncologie
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
• Taiwan
  • Tainan, Taiwan, 00704
    • National Cheng Kung Univ Hosp
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 112
    • Taipei Veterans General Hospital
  • Xitun Dist., Taiwan, 40705
    • Taichung Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • National Cancer Inst.
  • Chiang Rai, Thailand, 57000
    • Chiang Rai Prachanukroh Hospital; Department Of Medicine
  • Khonkaen, Thailand, 40000
    • Khonkaen Hospital
  • Patumwan, Thailand, 10330
    • King Chulalongkorn Memorial Hospital; Faculty of Medicine Chulalongkorn University
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory
• Turkey
  • Adana, Turkey, 01230
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
  • Ankara, Turkey, 06100
    • Ankara University Medical Faculty; Medikal Onkoloji
  • Edirne, Turkey, 22770
    • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
  • Malatya, Turkey, 44280
    • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Dnipropetrovsk State Medical Academy; Chemotherapy Department
  • Kharkiv, Ukraine, 61070
    • Karkiv Regional Oncology Center
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Oncological Dispensary
  • Lviv, Ukraine, 79031
    • Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital; Dept of Oncology
  • London, United Kingdom, SE1 9RT
    • Guys & St Thomas Hospital; Department of Oncology
  • London, United Kingdom, N7 9NH
    • University College London Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • Northridge, California, United States, 91328
      • North Valley Hem Onc Med Grp; Thomas&Dorothy Leavey Can Ctr
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center; UC Irvine Medical Center
    • Redondo Beach, California, United States, 90277
      • TMPN/ Cancer Care Associates
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family CCC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Hospital Regional Cancer Center
    • Greeley, Colorado, United States, 85234
      • Banner MD Anderson Cancer Center
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami-Deerfield Beach
    • Orlando, Florida, United States, 32804
      • Cancer Institute of Florida PA
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Health Care System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr; Hem/Onc
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Can Ins
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Uni School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Center - Peak
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
  • Texas
    • Dallas, Texas, United States, 75390-8813
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test
• Life expectancy of at least 12 weeks
• Eastern cooperative oncology group performance status (ECOG PS) of 0-2
• Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
• Adequate renal, and hematologic function
• Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
• Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment
• Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline)
• Negative pregnancy test for all females of child bearing potential
• Use of highly effective contraception as defined by the study protocol

Exclusion Criteria:

• Participants with a previous malignancy within the past 3 years
• Any gastrointestinal (GI) disorder or liver disease
• National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia)
• History of organ transplant
• Co-administration of anti-cancer therapies other than those administered in this study
• Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia
• Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment
• Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only
• History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation
• Pregnancy or lactation
• Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alectinib; Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Alectinib; Participants will receive alectinib 600 mg orally (four 150 mg capsules) BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.; Other Names: RO5424802
Active Comparator: Crizotinib; Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Crizotinib; Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) by Investigator Assessment	PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Percentage of Participants With PFS Event by Investigator Assessment	PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS Independent Review Committee (IRC)-Assessed	PFS was assessed as time to disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Percentage of Participants With PFS Event by IRC	PFS was assessed as percentage of participants with disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria	CNS progression was assessed as percentage of participants with an event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria	CNS progression was assessed as percentage of participants with event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria	ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators	DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 43 months)
Percentage of Participants With OS Event	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 43 months)
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria	CNS ORR was defined as the percentage of participants who attained CR or PR and had measurable/non-measurable CNS lesions at baseline. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
CNS DOR IRC-assessed According to RECIST v1.1 Criteria	CNS DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Percentage of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm
Area Under The Concentration-Time Curve (AUC) of Alectinib		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Maximum Concentration (Cmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Reach Cmax (Tmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
AUC of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Cmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Tmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Dziadziuszko R, Peters S, Mok T, Camidge DR, Gadgeel SM, Ou SI, Konopa K, Noe J, Nowicka M, Bordogna W, Morcos PN, Smoljanovic V, Shaw AT. Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial. Clin Cancer Res. 2022 May 2;28(9):1800-1808. doi: 10.1158/1078-0432.CCR-21-2840.
• Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Perol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanovic V, Hilton M, Ruf T, Noe J, Peters S. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020 Aug;31(8):1056-1064. doi: 10.1016/j.annonc.2020.04.478. Epub 2020 May 11.
• Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Perol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nuesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. doi: 10.1093/annonc/mdy405.
• Burudpakdee C, Wong W, Seetasith A, Corvino FA, Yeh W, Gubens M. Economic impact of preventing brain metastases with alectinib in ALK-positive non-small cell lung cancer. Lung Cancer. 2018 May;119:103-111. doi: 10.1016/j.lungcan.2018.03.008. Epub 2018 Mar 9.
• Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2014
• Primary Completion (Actual): February 9, 2017
• Study Completion (Estimated): September 29, 2026

Study Registration Dates

• First Submitted: February 27, 2014
• First Submitted That Met QC Criteria: February 27, 2014
• First Posted (Estimated): March 3, 2014

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: BO28984; 2013-004133-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No