TriangleNCT02075840 · CITED IN SOURCE DOCUMENTS
A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2026-05-29
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS) by Investigator Assessment
Percentage of Participants With PFS Event by Investigator Assessment
PFS Independent Review Committee (IRC)-Assessed
Percentage of Participants With PFS Event by IRC
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria
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
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators
Overall Survival (OS)
Percentage of Participants With OS Event
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria
CNS DOR IRC-assessed According to RECIST v1.1 Criteria
Percentage of Participants With Adverse Events
Area Under The Concentration-Time Curve (AUC) of Alectinib
Maximum Concentration (Cmax) of Alectinib
Time to Reach Cmax (Tmax) of Alectinib
AUC of Alectinib Metabolite
Cmax of Alectinib Metabolite
Tmax of Alectinib Metabolite
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
- intervention Names
- Drug: Alectinib
- label
- Alectinib
- type
- EXPERIMENTAL
- description
- Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
- intervention Names
- Drug: Crizotinib
- label
- Crizotinib
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Alectinib
- description
- 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.
- name
- Alectinib
- other Names
- RO5424802
- type
- DRUG
- arm Group Labels
- Crizotinib
- description
- Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
- name
- Crizotinib
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 303
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Progression-Free Survival (PFS) by Investigator Assessment
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Percentage of Participants With PFS Event by Investigator Assessment
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- secondary Outcomes
- description
- 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.
- measure
- PFS Independent Review Committee (IRC)-Assessed
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Percentage of Participants With PFS Event by IRC
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria
- time Frame
- Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria
- time Frame
- Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- 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
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators
- time Frame
- First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to approximately 10 years)
- description
- Overall survival (OS) was defined as the time from randomization to death from any cause.
- measure
- Overall Survival (OS)
- time Frame
- From randomization until death (up to 10.5 years)
- description
- Overall survival (OS) was defined as the time from randomization to death from any cause.
- measure
- Percentage of Participants With OS Event
- time Frame
- From randomization until death (up to 10.5 years)
- description
- 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.
- measure
- Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria
- time Frame
- Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- CNS DOR IRC-assessed According to RECIST v1.1 Criteria
- time Frame
- First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
- description
- 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.
- measure
- Percentage of Participants With Adverse Events
- time Frame
- Baseline up to approximately 10 years
- measure
- Area Under The Concentration-Time Curve (AUC) of Alectinib
- time Frame
- 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)
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- Sikkema BJ, Baart SJ, Paats MS, Smit EF, Schols AMWJ, Mathijssen RHJ, van Rossum EFC, Dingemans AC. Body Weight Gain Associated With Alectinib in Patients With ALK+ Non-Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials. J Clin Oncol. 2025 Feb 20;43(6):641-650. doi: 10.1200/JCO-24-01579. Epub 2024 Dec 11.
- pmid
- 39661917
- type
- DERIVED
- citation
- 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.
- pmid
- 35275991
- type
- DERIVED
- citation
- 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.
- pmid
- 32418886
- type
- DERIVED
- citation
- 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.
- pmid
- 30215676
- type
- DERIVED
- citation
- 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.
- pmid
- 29656744
- type
- DERIVED
- citation
- 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.
- pmid
- 28586279
- type
- DERIVED
- 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.
- pmid
- 28501139
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice