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Trial record 19 of 39 for:    ALECTINIB

Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib

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ClinicalTrials.gov Identifier: NCT02604342
Recruitment Status : Completed
First Posted : November 13, 2015
Results First Posted : February 26, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Alectinib
Drug: Docetaxel
Drug: Pemetrexed
Enrollment 107
Recruitment Details The study recruited participants with Anaplastic Lymphoma Kinase (ALK)-positive advanced Non-Small Cell Lung Cancer (NSCLC) in 13 countries from November 2015 to January 2017.
Pre-assignment Details A total of 107 participants were randomized at the time of clinical cut-off (CCO) date included in the intent-to-treat (ITT) population; 72 participants in the alectinib arm and 35 participants in the chemotherapy arm.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Period Title: Overall Study
Started 72 35
Completed 0 0
Not Completed 72 35
Reason Not Completed
Death             16             7
Progression of disease             1             0
Withdrawal by Subject             3             3
Ongoing             52             25
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel Total
Hide Arm/Group Description Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously. Total of all reporting groups
Overall Number of Baseline Participants 72 35 107
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants randomized in the study, irrespective of whether or not they received study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 35 participants 107 participants
54.5  (12.6) 58.8  (10.4) 55.9  (12.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 35 participants 107 participants
Female
31
  43.1%
18
  51.4%
49
  45.8%
Male
41
  56.9%
17
  48.6%
58
  54.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 35 participants 107 participants
Hispanic or Latino 5 4 9
Not Hispanic or Latino 61 29 90
Not reported 4 1 5
Unknown 0 1 1
Missing 2 0 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 35 participants 107 participants
White 61 28 89
Asian 5 7 12
Unknown 5 0 5
Native Hawaiian or other Pacific Islander 1 0 1
1.Primary Outcome
Title Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
Hide Description PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
9.6
(6.9 to 12.2)
1.4
(1.3 to 1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Alectinib, Active Comparator: Premetrexed/Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.08 to 0.29
Estimation Comments Estimated hazard ratio obtained from stratified Cox model with treatment group as covariate.
2.Secondary Outcome
Title Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
Hide Description Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with measurable CNS metastasis (mc-ITT) included all participants in ITT population with measurable CNS metastasis at baseline (as per IRC).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 24 16
Measure Type: Number
Unit of Measure: percentage of participants
54.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Alectinib, Active Comparator: Premetrexed/Docetaxel
Comments 95% confidence interval of the difference (alectinib - chemotherapy) computed using Hauck-Anderson approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in C-ORR
Estimated Value 0.542
Confidence Interval (2-Sided) 95%
0.23 to 0.78
Estimation Comments [Not Specified]
3.Secondary Outcome
Title PFS Using RECIST Version 1.1 as Assessed by IRC
Hide Description PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
7.1
(6.3 to 10.8)
1.6
(1.3 to 4.1)
4.Secondary Outcome
Title Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
Hide 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Measure Type: Number
Unit of Measure: percentage of participants
Assessed by Investigator 37.5 2.9
Assessed by IRC 36.1 11.4
5.Secondary Outcome
Title Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
Hide Description Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. 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, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Measure Type: Number
Unit of Measure: percentage of participants
Assessed by Investigator 80.6 28.6
Assessed by IRC 76.4 48.6
6.Secondary Outcome
Title Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
Hide 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until PD, death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants with a BOR of CR or PR.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
Assessed by Investigator Number Analyzed 27 participants 1 participants
9.3 [1] 
(6.9 to NA)
2.7 [2] 
(NA to NA)
Assessed by IRC Number Analyzed 26 participants 4 participants
9.7 [3] 
(5.6 to NA)
NA [2] 
(NA to NA)
[1]
The upper limit of confidence interval (CI) was not reached due to less number of participants with the event.
[2]
The CI was not reached due to less number of participants with the event.
[3]
The upper limit of CI was not reached due to less number of participants with the event.
7.Secondary Outcome
Title PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
Hide Description PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with CNS metastasis (C-ITT) included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
Assessed by Investigator
9.7 [1] 
(6.9 to NA)
1.4
(1.2 to 1.6)
Assessed by IRC
8.1 [1] 
(6.3 to NA)
1.5
(1.2 to 4.1)
[1]
The upper limit of CI was not reached due to less number of participants with the event.
8.Secondary Outcome
Title Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Hide Description Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(6.8 to NA)
1.6
(1.3 to 9.9)
[1]
The median and upper limit of CI was not reached due to less number of participants with the event.
9.Secondary Outcome
Title Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Hide Description Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. 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, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Measure Type: Number
Unit of Measure: percentage of participants
80.0 26.9
10.Secondary Outcome
Title Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Hide 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.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Measure Type: Number
Unit of Measure: percentage of participants
36.0 0.0
11.Secondary Outcome
Title Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
Hide 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. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.
Time Frame Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants with a BOR of CR or PR.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(6.2 to NA)
NA [2] 
(NA to NA)
[1]
The value of median and upper limit of CI was not reached due to less number of participants with event.
[2]
No participant had best overall response of CR or PR.
12.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.
Time Frame Approximately 15 months (Baseline until death)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
12.6 [1] 
(9.7 to NA)
NA [2] 
(NA to NA)
[1]
The upper limit of CI was not reached due to less number of participants with the event.
[2]
The median and CI was not reached due to less number of participants with the event.
13.Secondary Outcome
Title Plasma Concentration of Alectinib
Hide Description [Not Specified]
Time Frame Predose (2 hours) at Baseline, Week 3 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.
Arm/Group Title Experimental: Alectinib
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 56
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram/milliliter (ng/mL)
559
(48.0%)
14.Secondary Outcome
Title Plasma Concentration of Alectinib Metabolite
Hide Description [Not Specified]
Time Frame Predose (2 hours) at Baseline, Week 3 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.
Arm/Group Title Experimental: Alectinib
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 56
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
240
(44.8%)
15.Secondary Outcome
Title Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Hide Description Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. 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.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Measure Type: Number
Unit of Measure: percentage of participants
Baseline 91.7 88.6
Treatment - Week 3 94.0 81.8
Treatment - Week 6 95.2 64.3
Treatment - Week 12 92.5 77.8
Treatment - Week 18 76.7 66.7
Treatment - Week 24 88.2 100
Treatment - Week 30 88.0 66.7
Treatment - Week 36 89.5 50
Treatment - Week 42 100 50
Treatment - Week 48 85.7 NA [1] 
Treatment - Week 54 100 NA [1] 
Treatment - Week 60 50 NA [1] 
[1]
No participant was evaluated
16.Secondary Outcome
Title Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Hide Description Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. 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.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Measure Type: Number
Unit of Measure: percentage of participants
Baseline 91.7 85.7
Treatment - Week 3 94 81.8
Treatment - Week 6 95.2 67.9
Treatment - Week 12 92.5 77.8
Treatment - Week 18 76.7 66.7
Treatment - Week 24 88.2 100
Treatment - Week 30 88.0 66.7
Treatment - Week 36 89.5 50
Treatment - Week 42 100 50
Treatment - Week 48 85.7 NA [1] 
Treatment - Week 54 100 NA [1] 
Treatment - Week 60 50 NA [1] 
[1]
No participant was evaluated
17.Secondary Outcome
Title Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Hide Description Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Measure Type: Number
Unit of Measure: percentage of participants
Treatment - Week 0 Number Analyzed 72 participants 35 participants
88.9 82.9
Treatment - Week 3 Number Analyzed 67 participants 33 participants
86.6 78.8
Treatment - Week 6 Number Analyzed 62 participants 29 participants
91.9 58.6
Treatment - Week 12 Number Analyzed 53 participants 10 participants
86.8 80
Treatment - Week 18 Number Analyzed 43 participants 6 participants
72.1 66.7
Treatment - Week 24 Number Analyzed 34 participants 3 participants
82.4 100
Treatment - Week 30 Number Analyzed 25 participants 3 participants
80 66.7
Treatment - Week 36 Number Analyzed 20 participants 2 participants
80 50
Treatment - Week 42 Number Analyzed 12 participants 2 participants
91.7 50
Treatment - Week 48 Number Analyzed 8 participants 1 participants
62.5 0
Treatment - Week 54 Number Analyzed 3 participants 0 participants
100
Treatment - Week 60 Number Analyzed 2 participants 0 participants
50
18.Secondary Outcome
Title Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
Hide Description TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants evaluated for specified categories.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
Coughing score
NA [1] 
(6.7 to NA)
NA [2] 
(NA to NA)
Dyspnoea score
2.8 [3] 
(0.9 to NA)
4.2 [3] 
(1.2 to NA)
Pain in chest score
NA [1] 
(8.1 to NA)
NA [1] 
(2.0 to NA)
Pain in arm or shoulder score
8.1 [3] 
(4.1 to NA)
1.9 [3] 
(1.6 to NA)
[1]
The median and upper limit of CI was not reached due to less number of participants with the event.
[2]
The median and CI was not reached due to less number of participants with the event.
[3]
The upper limit of CI was not reached due to less number of participants with the event.
19.Secondary Outcome
Title Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
Hide Description TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants evaluated for specified categories.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
Coughing score
NA [1] 
(5.6 to NA)
NA [2] 
(NA to NA)
Dyspnoea score
4.1 [3] 
(0.9 to NA)
1.6 [3] 
(0.8 to NA)
Pain in chest score
NA [1] 
(8.1 to NA)
NA [1] 
(1.4 to NA)
Pain in arm or shoulder score
7.4 [3] 
(4.1 to NA)
1.7 [3] 
(0.9 to NA)
[1]
The median and upper limit of CI was not reached due to less number of participants with the event.
[2]
The median and CI was not reached due to less number of participants with the event.
[3]
The upper limit of CI was not reached due to less number of participants with the event.
20.Secondary Outcome
Title Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
Hide Description TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
Dyspnoea score
NA [1] 
(2.8 to NA)
NA [1] 
(1.2 to NA)
Fatigue score
2.7
(1.4 to 9.7)
1.4 [2] 
(0.8 to NA)
[1]
The median and upper limit of CI was not reached due to less number of participants with the event.
[2]
The upper limit of CI was not reached due to less number of participants with the event.
21.Secondary Outcome
Title Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
Hide Description TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
Dyspnoea score
NA [1] 
(2.9 to NA)
NA [1] 
(1.2 to NA)
Fatigue score
8.5 [2] 
(1.5 to NA)
1.2 [2] 
(0.8 to NA)
[1]
The median and upper limit of CI was not reached due to less number of participants with the event.
[2]
The upper limit of CI was not reached due to less number of participants with the event.
22.Secondary Outcome
Title TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
Hide Description TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 50 26
Median (95% Confidence Interval)
Unit of Measure: months
1.8
(0.9 to 4.1)
1.6 [1] 
(0.8 to NA)
[1]
The upper limit of CI was not reached due to less number of participants with the event.
23.Secondary Outcome
Title TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
Hide Description TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
Time Frame Approximately 15 months (baseline, Weeks 3, 6, 12 and every 6 weeks until PD, death, or withdrawal from study prior to PD)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 72 35
Median (95% Confidence Interval)
Unit of Measure: months
1.4
(0.9 to 2.9)
1.6 [1] 
(0.9 to NA)
[1]
The upper limit of CI was not reached due to less number of participants with the event.
24.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide 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.
Time Frame Approximately 15 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) population included all participants who received at least one dose of any study drug.
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description:
Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Overall Number of Participants Analyzed 70 34
Measure Type: Number
Unit of Measure: Percentage of Participants
77.1 85.3
Time Frame Approximately 15 months
Adverse Event Reporting Description SAF population included all participants who received at least one dose of any study drug.
 
Arm/Group Title Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Hide Arm/Group Description Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
All-Cause Mortality
Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   14/70 (20.00%)   4/34 (11.76%) 
Show Serious Adverse Events Hide Serious Adverse Events
Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   13/70 (18.57%)   5/34 (14.71%) 
Blood and lymphatic system disorders     
Anaemia  1  0/70 (0.00%)  1/34 (2.94%) 
Febrile neutropenia  1  0/70 (0.00%)  1/34 (2.94%) 
Neutropenia  1  0/70 (0.00%)  1/34 (2.94%) 
Cardiac disorders     
Myocardial infarction  1  1/70 (1.43%)  0/34 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/70 (0.00%)  1/34 (2.94%) 
Diarrhoea  1  0/70 (0.00%)  1/34 (2.94%) 
Nausea  1  0/70 (0.00%)  1/34 (2.94%) 
Stomatitis  1  0/70 (0.00%)  1/34 (2.94%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/70 (1.43%)  0/34 (0.00%) 
Infections and infestations     
Abscess jaw  1  1/70 (1.43%)  0/34 (0.00%) 
Bronchitis  1  1/70 (1.43%)  0/34 (0.00%) 
Lung infection  1  0/70 (0.00%)  1/34 (2.94%) 
Pneumonia  1  2/70 (2.86%)  0/34 (0.00%) 
Pneumonia bacterial  1  0/70 (0.00%)  1/34 (2.94%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/70 (1.43%)  0/34 (0.00%) 
Jaw fracture  1  1/70 (1.43%)  0/34 (0.00%) 
Skull fractured base  1  1/70 (1.43%)  0/34 (0.00%) 
Wound dehiscence  1  1/70 (1.43%)  0/34 (0.00%) 
Investigations     
Blood creatine phosphokinase increased  1  1/70 (1.43%)  0/34 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Invasive ductal breast carcinoma  1  1/70 (1.43%)  0/34 (0.00%) 
Nervous system disorders     
Brain oedema  1  1/70 (1.43%)  0/34 (0.00%) 
Cerebellar ataxia  1  1/70 (1.43%)  0/34 (0.00%) 
Epilepsy  1  1/70 (1.43%)  0/34 (0.00%) 
Syncope  1  1/70 (1.43%)  0/34 (0.00%) 
Psychiatric disorders     
Depression  1  1/70 (1.43%)  0/34 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  2/70 (2.86%)  0/34 (0.00%) 
Renal disorder  1  1/70 (1.43%)  0/34 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  1  1/70 (1.43%)  0/34 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/70 (1.43%)  0/34 (0.00%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental: Alectinib Active Comparator: Premetrexed/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   36/70 (51.43%)   25/34 (73.53%) 
Blood and lymphatic system disorders     
Anaemia  1  10/70 (14.29%)  3/34 (8.82%) 
Neutropenia  1  2/70 (2.86%)  4/34 (11.76%) 
Gastrointestinal disorders     
Constipation  1  13/70 (18.57%)  4/34 (11.76%) 
Diarrhoea  1  2/70 (2.86%)  2/34 (5.88%) 
Nausea  1  1/70 (1.43%)  5/34 (14.71%) 
Vomiting  1  2/70 (2.86%)  2/34 (5.88%) 
General disorders     
Asthenia  1  7/70 (10.00%)  5/34 (14.71%) 
Fatigue  1  4/70 (5.71%)  9/34 (26.47%) 
Oedema peripheral  1  6/70 (8.57%)  2/34 (5.88%) 
Pyrexia  1  2/70 (2.86%)  3/34 (8.82%) 
Investigations     
Blood bilirubin increased  1  4/70 (5.71%)  0/34 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  5/70 (7.14%)  3/34 (8.82%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  4/70 (5.71%)  2/34 (5.88%) 
Myalgia  1  6/70 (8.57%)  3/34 (8.82%) 
Pain in extremity  1  0/70 (0.00%)  2/34 (5.88%) 
Nervous system disorders     
Dizziness  1  2/70 (2.86%)  2/34 (5.88%) 
Headache  1  3/70 (4.29%)  2/34 (5.88%) 
Neuropathy peripheral  1  1/70 (1.43%)  2/34 (5.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/70 (4.29%)  3/34 (8.82%) 
Dyspnoea  1  6/70 (8.57%)  0/34 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  0/70 (0.00%)  6/34 (17.65%) 
Pruritus  1  0/70 (0.00%)  3/34 (8.82%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 1-800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02604342     History of Changes
Other Study ID Numbers: MO29750
2015-000634-29 ( EudraCT Number )
First Submitted: November 11, 2015
First Posted: November 13, 2015
Results First Submitted: January 24, 2018
Results First Posted: February 26, 2018
Last Update Posted: October 23, 2018