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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/NCT02075840




Registration number
NCT02075840
Ethics application status
Date submitted
27/02/2014
Date registered
3/03/2014
Date last updated
14/05/2024

Titles & IDs
Public title
A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants
Scientific title
Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
2013-004133-33
Secondary ID [2] 0 0
BO28984
Universal Trial Number (UTN)
Trial acronym
ALEX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
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 - Alectinib
Treatment: Drugs - Crizotinib

Experimental: Alectinib - Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Active Comparator: Crizotinib - Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.


Treatment: Drugs: 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.

Treatment: Drugs: Crizotinib
Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) 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) by Investigator Assessment
Timepoint [1] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Primary outcome [2] 0 0
Percentage of Participants With PFS Event by Investigator Assessment
Timepoint [2] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [1] 0 0
PFS Independent Review Committee (IRC)-Assessed
Timepoint [1] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [2] 0 0
Percentage of Participants With PFS Event by IRC
Timepoint [2] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [3] 0 0
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria
Timepoint [3] 0 0
Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)
Secondary outcome [4] 0 0
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria
Timepoint [4] 0 0
Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [6] 0 0
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators
Timepoint [6] 0 0
First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
From randomization until death (up to 43 months)
Secondary outcome [8] 0 0
Percentage of Participants With OS Event
Timepoint [8] 0 0
From randomization until death (up to 43 months)
Secondary outcome [9] 0 0
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria
Timepoint [9] 0 0
Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [10] 0 0
CNS DOR IRC-assessed According to RECIST v1.1 Criteria
Timepoint [10] 0 0
First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary outcome [11] 0 0
Percentage of Participants With Adverse Events
Timepoint [11] 0 0
Baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm
Secondary outcome [12] 0 0
Area Under The Concentration-Time Curve (AUC) of Alectinib
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Maximum Concentration (Cmax) of Alectinib
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Time to Reach Cmax (Tmax) of Alectinib
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
AUC of Alectinib Metabolite
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Cmax of Alectinib Metabolite
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Tmax of Alectinib Metabolite
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)
Timepoint [18] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [19] 0 0
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)
Timepoint [19] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [20] 0 0
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Timepoint [20] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [21] 0 0
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Timepoint [21] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [22] 0 0
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score
Timepoint [22] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [23] 0 0
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing
Timepoint [23] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [24] 0 0
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea
Timepoint [24] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [25] 0 0
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest
Timepoint [25] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary outcome [26] 0 0
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder
Timepoint [26] 0 0
Baseline, every 4 weeks until disease progression (up to 33 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/08/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/09/2026
Actual
Sample size
Target
Accrual to date
Final
303
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Royal North Shore Hospital; Oncology - St. Leonards
Recruitment hospital [3] 0 0
Calvary Mater Newcastle; Medical Oncology - Waratah
Recruitment hospital [4] 0 0
Queen Elizabeth Hospital; Medical Oncology - Woodville South
Recruitment hospital [5] 0 0
Monash Health Translational Precinct; Clinical Trials Centre, Level 3 - Victoria
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
5011 - Woodville South
Recruitment postcode(s) [5] 0 0
3168 - Victoria
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
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
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Massachusetts
Country [8] 0 0
United States of America
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Michigan
Country [9] 0 0
United States of America
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Missouri
Country [10] 0 0
United States of America
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Nevada
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United States of America
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New York
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United States of America
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Tennessee
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United States of America
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Texas
Country [14] 0 0
Bosnia and Herzegovina
State/province [14] 0 0
Banja Luka
Country [15] 0 0
Bosnia and Herzegovina
State/province [15] 0 0
Sarajevo
Country [16] 0 0
Brazil
State/province [16] 0 0
RS
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
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Canada
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Ontario
Country [20] 0 0
Canada
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Saskatchewan
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Chile
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Recoleta
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China
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Guangzhou City
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China
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Shanghai
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Costa Rica
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San José
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Egypt
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Cairo
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France
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Grenoble
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France
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Lille
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France
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Lyon
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France
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Pessac
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France
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Rennes
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Germany
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Karlsruhe
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Germany
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Löwenstein
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Guatemala
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Guatemala City
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Hong Kong
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Hong Kong
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Hong Kong
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Shatin
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Israel
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Haifa
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Israel
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Kfar-Saba
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Italy
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Campania
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Italy
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Emilia-Romagna
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Piemonte
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Italy
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Puglia
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Italy
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Sicilia
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Italy
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Umbria
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Mexico
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Mexico CITY (federal District)
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New Zealand
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Auckland
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Poland
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Gdansk
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Poland
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Lublin
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Poland
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Olsztyn
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Poland
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Otwock
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Poland
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Warszawa
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Russian Federation
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Kaluga
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Russian Federation
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Moskovskaja Oblast
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Russian Federation
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Sankt Petersburg
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Russian Federation
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Novosibirsk
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Serbia
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Belgrade
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Serbia
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Sremska Kamenica
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Singapore
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Singapore
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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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Sevilla
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Switzerland
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Basel
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Switzerland
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Bern
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Switzerland
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Lausanne
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Switzerland
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Zürich
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Taiwan
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Tainan
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Taiwan
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Taipei City
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Taiwan
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Taipei
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Taiwan
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Xitun Dist.
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Thailand
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Bangkok
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Thailand
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Chiang Rai
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Thailand
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Khonkaen
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Thailand
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Patumwan
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Thailand
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Songkhla
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Malatya
Country [87] 0 0
Ukraine
State/province [87] 0 0
Dnipropetrovsk
Country [88] 0 0
Ukraine
State/province [88] 0 0
Kharkiv
Country [89] 0 0
Ukraine
State/province [89] 0 0
Kyiv
Country [90] 0 0
Ukraine
State/province [90] 0 0
Lviv
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Birmingham
Country [92] 0 0
United Kingdom
State/province [92] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02075840
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02075840