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A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment

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ClinicalTrials.gov Identifier: NCT01801111
Recruitment Status : Completed
First Posted : February 28, 2013
Results First Posted : May 26, 2016
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small-Cell Lung Carcinoma
Interventions Drug: Erlotinib
Drug: Alectinib
Enrollment 138
Recruitment Details Overall study status was confirmed as completed. Here, 'study terminated by sponsor' in reason for study not completed means participants were transitioned to commercial supply of alectinib (where it was available) or transitioned to a roll-over study BO39694 (NCT03194893) where they continued to receive alectinib treatment.
Pre-assignment Details Part 1 of study was planned to determine recommended Phase 2 dose (RP2D) of alectinib to be used in Part 2. During the conduct of Part 1 for this study, RP2D was confirmed in Study NP28761 (NCT01871805). Hence Part 1 participants were merged into Part 2. Part 3 was post-progression treatment period.
Arm/Group Title Alectinib
Hide Arm/Group Description Participants received alectinib at a dose of 600 milligrams (mg) via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until disease progression (PD), death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Period Title: Overall Study
Started 138
Completed 0
Not Completed 138
Reason Not Completed
Adverse Event             12
Death             8
Physician Decision             5
Other             1
Withdrawal by Subject             4
Study Terminated by Sponsor             27
Progressive Disease             81
Arm/Group Title Alectinib
Hide Arm/Group Description Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Baseline Participants 138
Hide Baseline Analysis Population Description
Analysis was performed on safety population, which included all participants who received at least one dose of alectinib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 138 participants
51.5  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants
Female
77
  55.8%
Male
61
  44.2%
1.Primary Outcome
Title Recommended Phase 2 Dose (RP2D) of Alectinib
Hide Description RP2D was to be determined based on the safety and tolerability profile of the study treatment.
Time Frame Cycle 1 (up to 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805).
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Percentage of Participants With Dose Limiting Toxicities (DLTs)
Hide Description DLTs were to be assessed based on the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 (NCI-CTCAE v 4.3). DLTs: drug-related toxicities that meet any one of the following criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia continuing for greater than or equal to (>/=) 7 consecutive days or neutropenic fever; Non-hematological toxicity of Grade 3 or higher; Adverse events that require interruption of treatment for a total of >/=7 days.
Time Frame Cycle 1 (up to 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805).
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population
Hide Description Tumor response was assessed by IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to less than (<) 10 millimeters (mm). PR was defined as >/=30 percent (%) decrease in the sum of diameters (SoD) of target lesions (taking as reference the baseline SoD). The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (IRC) which included all participants with measurable disease at baseline according to the IRC, who had baseline tumor assessment and received at least one dose of alectinib.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50.8
(41.62 to 59.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib
Comments Tests null hypothesis that the objective response rate (ORR) is equal to 35% versus the alternative hypothesis that the objective response rate was not equal to 35%.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Exact Clopper-Pearson CI
Comments [Not Specified]
4.Primary Outcome
Title Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants
Hide Description Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR was defined as >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (IRC) participants who received prior chemotherapy.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.8
(34.63 to 55.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib
Comments Tests null hypothesis that the ORR is equal to 35% versus the alternative hypothesis that the objective response rate was not equal to 35%.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0599
Comments [Not Specified]
Method Exact Clopper-Pearson CI
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants
Hide Description Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR was defined as >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (IRC) participants who did not receive prior chemotherapy.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Measure Type: Number
Unit of Measure: percentage of participants
73.1
6.Secondary Outcome
Title Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR was defined as >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (Investigator) which included all participants with measurable disease at baseline according to the investigator, who had baseline tumor assessment and received at least one dose of alectinib.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
51.4
(42.80 to 60.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib
Comments Tests null hypothesis that the ORR is equal to 35% versus the alternative hypothesis that the objective response rate was not equal to 35%.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Exact Clopper-Pearson CI
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR was defined as >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (investigator) participants who received prior chemotherapy.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 110
Measure Type: Number
Unit of Measure: percentage of participants
50.0
8.Secondary Outcome
Title Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR was defined as >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (investigator) participants who did not receive prior chemotherapy.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: percentage of participants
57.1
9.Secondary Outcome
Title Duration of Response (DoR) as Assessed by IRC in RE Population
Hide Description DoR was defined as the time from the first observation of an objective tumor response (CR or PR) until first observation of progressive disease (PD) according to RECIST v1.1 or death from any cause. CR: disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR: >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). PD: >/=20% relative increase and >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. Duration of response was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who did not progress or die after a confirmed objective response were censored at the date of their last tumor assessment.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population (IRC) participants with documented objective response as assessed by IRC according to RECIST v1.1.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 62
Median (95% Confidence Interval)
Unit of Measure: months
15.2
(11.2 to 24.9)
10.Secondary Outcome
Title Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population
Hide Description According to RECIST v1.1, PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Measure Type: Number
Unit of Measure: percentage of participants
71.0
11.Secondary Outcome
Title Progression Free Survival (PFS) as Assessed by IRC in Safety Population
Hide Description PFS was defined as the time interval between the date of the first treatment and the date of PD or death from any cause, whichever occurred first. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who neither progressed nor died at the time of assessment or who were lost to follow-up were censored at the date of the last tumor assessment. Participants with no post-baseline assessments were censored at the date of first dose.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Median (95% Confidence Interval)
Unit of Measure: months
8.9
(5.6 to 12.8)
12.Secondary Outcome
Title Percentage of Participants Who Died of Any Cause
Hide Description Percentage of participants who died of any cause was reported.
Time Frame Baseline up to death from any cause (up to approximately 4 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Measure Type: Number
Unit of Measure: percentage of participants
54.3
13.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who did not die were censored at the date last known to be alive.
Time Frame Baseline up to death from any cause (up to approximately 4 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Median (95% Confidence Interval)
Unit of Measure: months
29.2
(21.5 to 44.4)
14.Secondary Outcome
Title Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population
Hide Description The disease control rate (DCR) was defined as the percentage of participants achieving CR, PR, or SD that lasted for at least 16 weeks. Tumor response was assessed by the investigator and IRC according to RECIST v1.1. CR: disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to <10 mm. PR: >/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). PD: >/=20% relative increase and >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD while on study. The 95% CI was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on RE population which included all participants with measurable disease at baseline, who had baseline tumor assessment, and who received at least one dose of alectinib. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
IRC Assessment Number Analyzed 122 participants
63.9
(54.75 to 72.43)
Investigator Assessment Number Analyzed 138 participants
69.6
(61.16 to 77.11)
15.Secondary Outcome
Title Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1
Hide Description CNS response was assessed by IRC according to RECIST v1.1. CNS Objective response was defined as percentage of participants with a CR or PR. CR was defined as disappearance of all CNS lesions. PR was defined as >/=30% decrease in the SoD of measurable CNS lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population participants with measurable CNS lesions at baseline.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.8
(40.70 to 75.35)
16.Secondary Outcome
Title Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria
Hide Description CNS response was assessed by IRC according to RANO criteria. CNS Objective response: percentage of participants with a CR or PR that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as complete disappearance of all enhancing measurable, non-measurable disease; stable or improved non-enhancing lesions; no new lesions; no corticosteroids (or only physiologic replacement dose), and clinically stable or improved. PR was defined as >/=50% decrease compared to screening in the sum of the products of the diameters (SPD) of enhancing measurable lesions; no progression of non-measurable disease (enhancing and non-enhancing lesions); no new lesions; no corticosteroids (or only physiologic replacement dose), and clinically stable or improved. The 95% CI was computed using Clopper-Pearson method.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population participants with measurable CNS lesions at baseline.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.1
(27.19 to 62.11)
17.Secondary Outcome
Title CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1
Hide Description CDoR was defined as the time from the first observation of a CNS objective response (CR or PR) until first observation of CNS progression as assessed by IRC according to RECIST v 1.1 or death from any cause. CR: disappearance of all CNS lesions. PR: >/=30% decrease in the SoD of measurable CNS lesions (taking as reference the baseline SoD). CNS progression: >/=20% increase in the SoD of measurable CNS lesions (with an absolute increase of at least 5 mm), taking as reference the baseline SoD; 1 or more new CNS lesion(s); and/or unequivocal progression of non-measurable CNS lesions. CDoR was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population participants with measurable CNS lesions at baseline and who had CNS objective response as assessed by IRC according to RECIST v1.1.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
11.1 [1] 
(7.1 to NA)
[1]
The upper limit of 95% CI could not be estimated due to high number of censored participants.
18.Secondary Outcome
Title CDoR as Assessed by IRC According to RANO Criteria
Hide Description CDoR: time from the CNS objective response until CNS progression as assessed by IRC according to RANO criteria or death from any cause. CR: complete disappearance of all enhancing measurable, non-measurable disease; stable/improved non-enhancing lesions; no new lesions; no corticosteroids, and clinically stable/improved. PR: >/=50% decrease compared to screening in SPD of enhancing measurable lesions; no progression of non-measurable disease; no new lesions; no corticosteroids, and clinically stable/improved. Progression: >/=25% increase in SPD of enhancing measurable lesions compared to best response on study; stable/increasing doses of corticosteroids; significant increase in non-enhancing lesions not caused by co-morbid events; any new lesions; progression of non-measurable disease; or clinical deterioration not attributable to other non-tumor causes. CDoR was estimated by Kaplan-Meier method and 95% CI was assessed using method of Brookmeyer and Crowley.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population participants with measurable CNS lesions at baseline and who had CNS objective response as assessed by IRC according to RANO criteria.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: months
7.6
(7.4 to 7.6)
19.Secondary Outcome
Title Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1
Hide Description According to RECIST v 1.1, CNS progression was defined as >/=20% increase in the SoD of measurable CNS lesions (with an absolute increase of at least 5 mm), taking as reference the baseline SoD; 1 or more new CNS lesion(s); and/or unequivocal progression of non-measurable CNS lesions.
Time Frame Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 138
Measure Type: Number
Unit of Measure: percentage of participants
18.8
20.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Alectinib
Hide Description Cmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 (Pharsight Corporation) software.
Time Frame Pre-dose (0 hours [hrs]), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Pharmacokinetic (PK) Evaluable Population, which included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1 Number Analyzed 28 participants
204
(47.6%)
Day 21 Number Analyzed 26 participants
933
(34.8%)
21.Secondary Outcome
Title Time to Cmax (Tmax) of Alectinib
Hide Description Tmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: hrs
Day 1 Number Analyzed 28 participants
5.89
(2.00 to 10.00)
Day 21 Number Analyzed 26 participants
4.12
(0.0 to 11.18)
22.Secondary Outcome
Title Time to Last Measurable Plasma Concentration (Tlast) of Alectinib
Hide Description Tlast for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs
Day 1 Number Analyzed 28 participants
11.59
(3.9%)
Day 21 Number Analyzed 26 participants
11.65
(3.8%)
23.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib
Hide Description The AUC(0-10) of alectinib was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs*nanograms per milliliter (hrs*ng/mL)
Day 1 Number Analyzed 28 participants
1140
(44.5%)
Day 21 Number Analyzed 26 participants
7860
(37.2%)
24.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib
Hide Description The AUC(0-last) of alectinib was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs*ng/mL
Day 1 Number Analyzed 28 participants
1340
(44.9%)
Day 21 Number Analyzed 26 participants
9090
(36.9%)
25.Secondary Outcome
Title Cmax of Alectinib Metabolite
Hide Description Cmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1 Number Analyzed 28 participants
57.2
(68.6%)
Day 21 Number Analyzed 26 participants
303
(33.5%)
26.Secondary Outcome
Title Tmax of Alectinib Metabolite
Hide Description Tmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: hrs
Day 1 Number Analyzed 28 participants
8.03
(5.97 to 11.18)
Day 21 Number Analyzed 26 participants
7.00
(0.0 to 12.00)
27.Secondary Outcome
Title Tlast of Alectinib Metabolite
Hide Description Tlast for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs
Day 1 Number Analyzed 28 participants
11.59
(3.9%)
Day 21 Number Analyzed 26 participants
11.65
(3.8%)
28.Secondary Outcome
Title AUC(0-10) of Alectinib Metabolite
Hide Description The AUC(0-10) of alectinib metabolite was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs*ng/mL
Day 1 Number Analyzed 28 participants
300
(68.4%)
Day 21 Number Analyzed 26 participants
2590
(35.0%)
29.Secondary Outcome
Title AUC(0-last) of Alectinib Metabolite
Hide Description The AUC(0-last) of alectinib metabolite was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hrs*ng/mL
Day 1 Number Analyzed 28 participants
378
(67.5%)
Day 21 Number Analyzed 26 participants
3040
(34.9%)
30.Secondary Outcome
Title Metabolite to Parent Ratio Based on AUC(0-10)
Hide Description Metabolite to parent ratio based on AUC(0-10) was computed as AUC(0-10) of metabolite divided by AUC(0-10) of parent drug (alectinib) corrected for the molecular weight of parent divided by the molecular weight of the metabolite.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
Day 1 Number Analyzed 28 participants
0.278
(41.0%)
Day 21 Number Analyzed 26 participants
0.349
(28.7%)
31.Secondary Outcome
Title Metabolite to Parent Ratio Based on AUC(0-last)
Hide Description Metabolite to parent ratio based on AUC(0-last) was computed as AUC(0-last) of metabolite divided by AUC(0-last) of parent drug (alectinib) corrected for the molecular weight of parent divided by the molecular weight of the metabolite.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Number Analyzed’=number of participant evaluable for specified category.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
Day 1 Number Analyzed 28 participants
0.298
(41.2%)
Day 21 Number Analyzed 26 participants
0.354
(28.7%)
32.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Alectinib
Hide Description [Not Specified]
Time Frame Pre-dose (0 hrs) on Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Overall Number of Participants Analyzed’=number of participant evaluable for this outcome measure.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
761
(42.9%)
33.Secondary Outcome
Title Ctrough of Alectinib Metabolite
Hide Description [Not Specified]
Time Frame Pre-dose (0 hrs) on Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Overall Number of Participants Analyzed’=number of participant evaluable for this outcome measure.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
244
(37.8%)
34.Secondary Outcome
Title Peak to Trough Ratio of Alectinib
Hide Description [Not Specified]
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Overall Number of Participants Analyzed’=number of participant evaluable for this outcome measure.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.23
(14.4%)
35.Secondary Outcome
Title Accumulation Ratio of Alectinib
Hide Description Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Overall Number of Participants Analyzed’=number of participant evaluable for this outcome measure.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
6.95
(42.1%)
36.Secondary Outcome
Title Accumulation Ratio of Alectinib Metabolite
Hide Description Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
Time Frame Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK Evaluable Population. Here, ‘Overall Number of Participants Analyzed’=number of participant evaluable for this outcome measure.
Arm/Group Title Alectinib
Hide Arm/Group Description:
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
8.68
(64.2%)
Time Frame From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Adverse Event Reporting Description Analysis was performed on safety population.
 
Arm/Group Title Alectinib
Hide Arm/Group Description Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
All-Cause Mortality
Alectinib
Affected / at Risk (%)
Total   75/138 (54.35%) 
Show Serious Adverse Events Hide Serious Adverse Events
Alectinib
Affected / at Risk (%)
Total   39/138 (28.26%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/138 (0.72%) 
Cardiac disorders   
Myocardial infarction * 1  1/138 (0.72%) 
Cardiac arrest * 1  1/138 (0.72%) 
Eye disorders   
Retinal detachment * 1  1/138 (0.72%) 
Gastrointestinal disorders   
Constipation * 1  2/138 (1.45%) 
Intestinal perforation * 1  1/138 (0.72%) 
Oesophagitis * 1  1/138 (0.72%) 
Vomiting * 1  1/138 (0.72%) 
Enterovesical fistula * 1  1/138 (0.72%) 
General disorders   
Malaise * 1  1/138 (0.72%) 
Hepatobiliary disorders   
Hyperbilirubinaemia * 1  3/138 (2.17%) 
Cholecystitis * 1  1/138 (0.72%) 
Infections and infestations   
Appendicitis perforated * 1  1/138 (0.72%) 
Intervertebral discitis * 1  1/138 (0.72%) 
Pleural infection * 1  1/138 (0.72%) 
Pneumonia * 1  2/138 (1.45%) 
Sepsis * 1  1/138 (0.72%) 
Appendicitis * 1  1/138 (0.72%) 
Bronchitis * 1  1/138 (0.72%) 
Endocarditis * 1  1/138 (0.72%) 
Enterocolitis infectious * 1  1/138 (0.72%) 
Infection * 1  1/138 (0.72%) 
Influenza * 1  1/138 (0.72%) 
Lower respiratory tract infection * 1  1/138 (0.72%) 
Lung infection * 1  1/138 (0.72%) 
Urosepsis * 1  1/138 (0.72%) 
Injury, poisoning and procedural complications   
Head injury * 1  1/138 (0.72%) 
Ligament rupture * 1  1/138 (0.72%) 
Investigations   
Alanine aminotransferase increased * 1  2/138 (1.45%) 
Aspartate aminotransferase increased * 1  2/138 (1.45%) 
International normalised ratio increased * 1  1/138 (0.72%) 
Musculoskeletal and connective tissue disorders   
Muscle haemorrhage * 1  1/138 (0.72%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer * 1  1/138 (0.72%) 
Nervous system disorders   
Seizure * 1  2/138 (1.45%) 
Psychiatric disorders   
Depression * 1  2/138 (1.45%) 
Renal and urinary disorders   
Ureterolithiasis * 1  1/138 (0.72%) 
Reproductive system and breast disorders   
Menorrhagia * 1  1/138 (0.72%) 
Pelvic floor muscle weakness * 1  1/138 (0.72%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  3/138 (2.17%) 
Epistaxis * 1  1/138 (0.72%) 
Haemoptysis * 1  1/138 (0.72%) 
Interstitial lung disease * 1  1/138 (0.72%) 
Pneumothorax * 1  1/138 (0.72%) 
Pulmonary embolism * 1  3/138 (2.17%) 
Pleural effusion * 1  1/138 (0.72%) 
Vascular disorders   
Haemorrhage * 1  1/138 (0.72%) 
1
Term from vocabulary, MedDRA v20.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alectinib
Affected / at Risk (%)
Total   133/138 (96.38%) 
Blood and lymphatic system disorders   
Anaemia * 1  19/138 (13.77%) 
Ear and labyrinth disorders   
Vertigo * 1  8/138 (5.80%) 
Gastrointestinal disorders   
Abdominal pain * 1  11/138 (7.97%) 
Abdominal pain upper * 1  17/138 (12.32%) 
Constipation * 1  53/138 (38.41%) 
Diarrhoea * 1  27/138 (19.57%) 
Nausea * 1  32/138 (23.19%) 
Vomiting * 1  22/138 (15.94%) 
Dyspepsia * 1  10/138 (7.25%) 
General disorders   
Asthenia * 1  31/138 (22.46%) 
Fatigue * 1  43/138 (31.16%) 
Oedema * 1  9/138 (6.52%) 
Oedema peripheral * 1  42/138 (30.43%) 
Pyrexia * 1  17/138 (12.32%) 
Chest pain * 1  10/138 (7.25%) 
Influenza like illness * 1  8/138 (5.80%) 
Infections and infestations   
Upper respiratory tract infection * 1  21/138 (15.22%) 
Bronchitis * 1  8/138 (5.80%) 
Influenza * 1  7/138 (5.07%) 
Sinusitis * 1  7/138 (5.07%) 
Urinary tract infection * 1  7/138 (5.07%) 
Viral upper respiratory tract infection * 1  15/138 (10.87%) 
Investigations   
Alanine aminotransferase increased * 1  15/138 (10.87%) 
Asparatate aminotransferase increased * 1  18/138 (13.04%) 
Blood bilirubin increased * 1  18/138 (13.04%) 
Blood creatinine increased * 1  7/138 (5.07%) 
Weight increased * 1  18/138 (13.04%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  17/138 (12.32%) 
Hypokalaemia * 1  7/138 (5.07%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  16/138 (11.59%) 
Back pain * 1  21/138 (15.22%) 
Bone pain * 1  8/138 (5.80%) 
Muscular weakness * 1  11/138 (7.97%) 
Musculoskeletal pain * 1  14/138 (10.14%) 
Myalgia * 1  36/138 (26.09%) 
Pain in extremity * 1  15/138 (10.87%) 
Muscle spasms * 1  10/138 (7.25%) 
Musculoskeletal chest pain * 1  8/138 (5.80%) 
Nervous system disorders   
Dizziness * 1  16/138 (11.59%) 
Headache * 1  27/138 (19.57%) 
Dysgeusia * 1  7/138 (5.07%) 
Paraesthesia * 1  7/138 (5.07%) 
Psychiatric disorders   
Insomnia * 1  14/138 (10.14%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  32/138 (23.19%) 
Dyspnoea * 1  22/138 (15.94%) 
Oropharyngeal pain * 1  16/138 (11.59%) 
Productive cough * 1  11/138 (7.97%) 
Dysphonia * 1  7/138 (5.07%) 
Nasal congestion * 1  7/138 (5.07%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  10/138 (7.25%) 
Dry skin * 1  13/138 (9.42%) 
Photosensitivity reaction * 1  16/138 (11.59%) 
Rash * 1  24/138 (17.39%) 
1
Term from vocabulary, MedDRA v20.0
*
Indicates events were collected by non-systematic assessment
Part 1 analysis was not conducted as during the conduct of the study the RP2D was confirmed in study NP28761 (NCT01871805).
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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01801111     History of Changes
Other Study ID Numbers: NP28673
2012-004455-36 ( EudraCT Number )
First Submitted: February 20, 2013
First Posted: February 28, 2013
Results First Submitted: August 19, 2015
Results First Posted: May 26, 2016
Last Update Posted: November 2, 2018