A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01801111
Collaborator
(none)
138
84
1
52.2
1.6
0
Study Details
Study Description
Brief Summary
This open-label, non-randomized, multicenter, Phase 1/2 study will evaluate the safety and efficacy of alectinib in participants with non-small cell lung cancer who have ALK mutation and failed crizotinib treatment. In Part 1, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Part 2, participants will receive the recommended phase 2 dose (RP2D) of alectinib as determined in Part 1. Treatment will continue in Part 1 and Part 2 on the same dose until disease progression. In Part 3, following disease progression, participants without epidermal growth factor receptor (EGFR) mutation will be offered continued treatment with alectinib, participants with EGFR mutations will be offered a combination of alectinib and erlotinib.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
138 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Non-Randomized, Multicenter Phase I/II Trial of RO5424802 Given Orally to Non-Small Cell Lung Cancer Patients Who Have ALK Mutation and Who Have Failed Crizotinib Treatment
Actual Study Start Date
:
Jun 20, 2013
Actual Primary Completion Date
:
Oct 24, 2014
Actual Study Completion Date
:
Oct 27, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Alectinib Participants will receive alectinib treatment continuously starting from Day 1 Cycle 1 (in 28-day cycles) until disease progression, death, or withdrawal for any other reasons, whichever occurs first. After PD, participants without EGFR mutation will continue treatment with alectinib alone and participants with EGFR mutation will receive alectinib in combination with erlotinib as per discretion of the treating physician. |
Drug: Erlotinib
Erlotinib will be administered at a dose of 100 mg via tablet, orally, once daily in combination with alectinib to participants who progressed on alectinib alone treatment as per treating physician discretion.
Other Names:
Drug: Alectinib
Alectinib will be administered at a dose of 600 milligrams (mg) via capsule, orally, twice daily.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) of Alectinib [Cycle 1 (up to 28 days)]
RP2D was to be determined based on the safety and tolerability profile of the study treatment.
- Percentage of Participants With Dose Limiting Toxicities (DLTs) [Cycle 1 (up to 28 days)]
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.
- 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 [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)]
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.
- Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants [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)]
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.
Secondary Outcome Measures
- Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants [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)]
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).
- Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population [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)]
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.
- Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants [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)]
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).
- Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants [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)]
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).
- Duration of Response (DoR) as Assessed by IRC in RE Population [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)]
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.
- Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population [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)]
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.
- Progression Free Survival (PFS) as Assessed by IRC in Safety Population [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)]
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.
- Percentage of Participants Who Died of Any Cause [Baseline up to death from any cause (up to approximately 4 years)]
Percentage of participants who died of any cause was reported.
- Overall Survival (OS) [Baseline up to death from any cause (up to approximately 4 years)]
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.
- Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population [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)]
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.
- Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1 [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)]
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.
- Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria [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)]
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.
- CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1 [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)]
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.
- CDoR as Assessed by IRC According to RANO Criteria [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)]
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.
- Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1 [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)]
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.
- Maximum Observed Plasma Concentration (Cmax) of Alectinib [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]
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 to Cmax (Tmax) of Alectinib [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]
Tmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
- Time to Last Measurable Plasma Concentration (Tlast) of Alectinib [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]
Tlast for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
- Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib [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]
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).
- Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib [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]
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).
- Cmax of Alectinib Metabolite [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]
Cmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
- Tmax of Alectinib Metabolite [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]
Tmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
- Tlast of Alectinib Metabolite [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]
Tlast for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
- AUC(0-10) of Alectinib Metabolite [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]
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).
- AUC(0-last) of Alectinib Metabolite [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]
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).
- Metabolite to Parent Ratio Based on AUC(0-10) [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]
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.
- Metabolite to Parent Ratio Based on AUC(0-last) [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]
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.
- Trough Plasma Concentration (Ctrough) of Alectinib [Pre-dose (0 hrs) on Day 21 of Cycle 1]
- Ctrough of Alectinib Metabolite [Pre-dose (0 hrs) on Day 21 of Cycle 1]
- Peak to Trough Ratio of Alectinib [Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 21 of Cycle 1]
- Accumulation Ratio of Alectinib [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]
Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
- Accumulation Ratio of Alectinib Metabolite [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]
Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by American Joint Committee on Cancer [AJCC])
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-
Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test
-
Prior treatment with crizotinib and progression according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria. Participants had to have a minimum 1-week wash-out period between the last dose of crizotinib and the first dose of study treatment. Participants can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
-
Adequate hematologic, hepatic, and renal function
-
Participants with brain or leptomeningeal metastases are allowed if protocol defined criteria are met
-
Measurable disease according to RECIST v1.1 prior to administration of first dose of study drug
Exclusion Criteria:
-
Receipt of any other ALK inhibitors in addition to crizotinib
-
Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to the first dose of study drug
-
Participants who received crizotinib or any other tyrosine kinase inhibitors need to have a minimum 1-week washout period before the first dose of study drug
-
Active or uncontrolled infectious diseases requiring treatment
-
National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade 3 or higher toxicities due to prior therapy that have not shown improvement and are considered to interfere with current study medication
-
History of organ transplant
-
Co-administration of anti-cancer therapies other than those administered in this study
-
Baseline corrected Q-T interval (QTc) greater than (>) 470 milliseconds, or baseline symptomatic bradycardia (less than 45 heart beats per minute)
-
Pregnant or breastfeeding women
-
Known Human Immunodeficiency Virus (HIV) positivity or Acquired Immunodeficiency Syndrome (AIDS)-related illness
-
History of hypersensitivity to any of the additives in the alectinib formulation
-
Any clinically significant concomitant disease or condition that could interfere with, or for which treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | St. Jude Heritage Healthcare | Fullerton | California | United States | 92835 |
| 3 | UC Irvine Medical Center | Orange | California | United States | 92868 |
| 4 | Sharp Memorial Hospital | San Diego | California | United States | 92123 |
| 5 | Coastal Integrative Cancer Care | San Luis Obispo | California | United States | 93401 |
| 6 | UCLA Cancer Center; Premiere Oncology, A Medical Corporation | Santa Monica | California | United States | 90404 |
| 7 | Advanced Medical Specialties | Miami | Florida | United States | 33176 |
| 8 | Florida Hospital Cancer Inst | Orlando | Florida | United States | 32804 |
| 9 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 10 | Midwestern Regional Medical Center; Office of Research | Zion | Illinois | United States | 60099 |
| 11 | Washington University; Wash Uni. Sch. Of Med | Saint Louis | Missouri | United States | 63110 |
| 12 | Comprehensive Cancer Centers of Nevada | Henderson | Nevada | United States | 89014 |
| 13 | Columbia University Medical Center; Department of Hematology/Oncology | New York | New York | United States | 10032 |
| 14 | University Hospitals Case Medical Center | Cleveland | Ohio | United States | 44106 |
| 15 | Texas Oncology, P.A. | Dallas | Texas | United States | 75246 |
| 16 | Cancer Care Centers of South Texas | San Antonio | Texas | United States | 78217 |
| 17 | Virginia Cancer Specialists, PC | Fairfax | Virginia | United States | 22031 |
| 18 | Royal North Shore Hospital | St. Leonards | New South Wales | Australia | 2065 |
| 19 | Prince Charles Hospital | Chermside | Queensland | Australia | 4032 |
| 20 | Townsville General Hospital | Douglas | Queensland | Australia | 4184 |
| 21 | UZ Antwerpen | Edegem | Belgium | 2650 | |
| 22 | UZ Gent | Gent | Belgium | 9000 | |
| 23 | AZ Delta (Campus Wilgenstraat) | Roeselare | Belgium | 8800 | |
| 24 | University Hospital Herlev | Herlev | Denmark | 2730 | |
| 25 | CHU Angers - Hôpital Hôtel Dieu | Angers | France | 49933 | |
| 26 | Hopital Morvan | Brest | France | 29200 | |
| 27 | Centre Francois Baclesse | Caen | France | 14076 | |
| 28 | Centre Georges François Leclerc; Service Pharmacie, Bp 77980 | Dijon | France | 21000 | |
| 29 | CHU de Grenoble - Hôpital Nord; Service d'Oncologie Thoracique | Grenoble | France | 38043 | |
| 30 | Centre Oscar Lambret | Lille | France | 59020 | |
| 31 | Centre Leon Berard | Lyon | France | 69008 | |
| 32 | Hôpital Nord - AP-HM Marseille#; Gastroenterology and Hepatology | Marseille cedex 20 | France | 13915 | |
| 33 | Groupe Hospitalier Sud - Hôpital Haut Lévêque | Pessac | France | 33600 | |
| 34 | Hopital Pontchaillou - CHU de Rennes | Rennes | France | 35033 | |
| 35 | ICO Rene Gauducheau; CEC | St Herblain | France | 44805 | |
| 36 | Nouvel Hopital Civil - CHU Strasbourg | Strasbourg | France | 67091 | |
| 37 | CHU de Toulouse - Hôpital Larrey | Toulouse | France | 31059 | |
| 38 | Charité Campus Virchow-Klinikum; Department of Cardiology | Berlin | Germany | 13353 | |
| 39 | Diakonie Kaiserswerth; Florence-Nightingale-Krankenhaus | Düsseldorf | Germany | 40489 | |
| 40 | LungenClinic Großhansdorf | Großhansdorf | Germany | 22927 | |
| 41 | Lungenklinik Hemer | Hemer | Germany | 58675 | |
| 42 | Klinikum Koeln-Merheim | Koeln | Germany | 51109 | |
| 43 | Mathias-Spital Rheine | Rheine | Germany | 48431 | |
| 44 | A.O. Universitaria Di Parma | Parma | Emilia-Romagna | Italy | 43100 |
| 45 | Irccs Centro Di Riferimento Oncologico (CRO) | Aviano | Friuli-Venezia Giulia | Italy | 33081 |
| 46 | Istituto Nazionale Tumori Regina Elena IRCCS | Roma | Lazio | Italy | 00144 |
| 47 | AO San Camillo Forlanini | Roma | Lazio | Italy | 00149 |
| 48 | Ospedale San Raffaele | Milano | Lombardia | Italy | 20132 |
| 49 | Istituto Europeo Di Oncologia | Milano | Lombardia | Italy | 20141 |
| 50 | Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda) | Milano | Lombardia | Italy | |
| 51 | Azienda Ospedaliera Universitaria Careggi | Firenze | Toscana | Italy | 50141 |
| 52 | Ospedale Versilia | Lido Di Camaiore | Toscana | Italy | 55043 |
| 53 | Presidio Ospedaliero Campo di Marte | Lucca | Toscana | Italy | 55100 |
| 54 | Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia | Perugia | Umbria | Italy | 06100 |
| 55 | National Cancer Center | Gyeonggi-do | Korea, Republic of | 10408 | |
| 56 | Seoul National University Bundang Hospital | Gyeonggi-do | Korea, Republic of | 13620 | |
| 57 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 58 | Severance Hospital, Yonsei University Health System; Pharmacy | Seoul | Korea, Republic of | 03722 | |
| 59 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 60 | Samsung Medical Center | Seoul | Korea, Republic of | 6351 | |
| 61 | Centre Hospitalier de Luxembourg | Luxembourg | Luxembourg | 1210 | |
| 62 | Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | Netherlands | 1066 CX | |
| 63 | Universitair Medisch Centrum Groningen | Groningen | Netherlands | 9713 GZ | |
| 64 | Maastricht University Medical Centre; Afdeling Klinische Farmacie en Toxicologie | Maastricht | Netherlands | 6229HX | |
| 65 | FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement | Moskva | Moskovskaja Oblast | Russian Federation | 115478 |
| 66 | National University Hospital; Investigational Medicine Unit | Singapore | Singapore | 119074 | |
| 67 | Johns Hopkins Singapore | Singapore | Singapore | 308433 | |
| 68 | Hospital General Univ. de Alicante | Alicante | Spain | 03010 | |
| 69 | Hospital del Mar | Barcelona | Spain | 08003 | |
| 70 | Hospital Universitario Quiron Dexeus | Barcelona | Spain | 08028 | |
| 71 | Hospital Clínic i Provincial de Barcelona | Barcelona | Spain | 08036 | |
| 72 | Hospital Universitario La Paz | Madrid | Spain | 280146 | |
| 73 | Hospital Universitario Ramón y Cajal | Madrid | Spain | 28034 | |
| 74 | Hospital Universitario Clínico San Carlos; Servicio de Oncologia | Madrid | Spain | 28040 | |
| 75 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 76 | Hospital Regional Universitario de Malaga | Malaga | Spain | 29010 | |
| 77 | Hosp Clinico Univ Lozano Blesa | Zaragoza | Spain | 50009 | |
| 78 | Karolinska | Stockholm | Sweden | 17176 | |
| 79 | Taichung Veterans General Hospital | Taichung | Taiwan | 407 | |
| 80 | National Cheng Kung Univ Hosp | Tainan | Taiwan | 00704 | |
| 81 | National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
| 82 | Aberdeen Royal Infirmary | Aberdeen | United Kingdom | AB25 2ZN | |
| 83 | Royal Marsden Hospital;Dept of Haematology Oncology Research | London | United Kingdom | SW3 6HP | |
| 84 | Royal Marsden Hospital - London | London | United Kingdom | SW3 6JJ |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01801111
Other Study ID Numbers:
- NP28673
- 2012-004455-36
First Posted:
Feb 28, 2013
Last Update Posted:
Nov 2, 2018
Last Verified:
Oct 1, 2018
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Alectinib |
|---|---|
| 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 Participants | 138 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
51.5
(11.1)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
77
55.8%
|
| Male |
61
44.2%
|
Outcome Measures
| Title | Recommended Phase 2 Dose (RP2D) of Alectinib |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805). |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Percentage of Participants With Dose Limiting Toxicities (DLTs) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805). |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 0 |
| 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 |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 122 |
| Number (95% Confidence Interval) [percentage of participants] |
50.8
36.8%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | Exact Clopper-Pearson CI | |
| Comments | ||
| Title | Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on RE population (IRC) participants who received prior chemotherapy. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 96 |
| Number (95% Confidence Interval) [percentage of participants] |
44.8
32.5%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | 0.0599 |
| Comments | ||
| Method | Exact Clopper-Pearson CI | |
| Comments | ||
| Title | Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on RE population (IRC) participants who did not receive prior chemotherapy. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 26 |
| Number [percentage of participants] |
73.1
53%
|
| Title | Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 138 |
| Number (95% Confidence Interval) [percentage of participants] |
51.4
37.2%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Exact Clopper-Pearson CI | |
| Comments | ||
| Title | Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on RE population (investigator) participants who received prior chemotherapy. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 110 |
| Number [percentage of participants] |
50.0
36.2%
|
| Title | Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on RE population (investigator) participants who did not receive prior chemotherapy. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Number [percentage of participants] |
57.1
41.4%
|
| Title | Duration of Response (DoR) as Assessed by IRC in RE Population |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 62 |
| Median (95% Confidence Interval) [months] |
15.2
|
| Title | Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 138 |
| Number [percentage of participants] |
71.0
51.4%
|
| Title | Progression Free Survival (PFS) as Assessed by IRC in Safety Population |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 138 |
| Median (95% Confidence Interval) [months] |
8.9
|
| Title | Percentage of Participants Who Died of Any Cause |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 138 |
| Number [percentage of participants] |
54.3
39.3%
|
| Title | Overall Survival (OS) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 138 |
| Median (95% Confidence Interval) [months] |
29.2
|
| Title | Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 138 |
| IRC Assessment |
63.9
46.3%
|
| Investigator Assessment |
69.6
50.4%
|
| Title | Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1 |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population participants with measurable CNS lesions at baseline. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
58.8
42.6%
|
| Title | Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population participants with measurable CNS lesions at baseline. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
44.1
32%
|
| Title | CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1 |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 20 |
| Median (95% Confidence Interval) [months] |
11.1
|
| Title | CDoR as Assessed by IRC According to RANO Criteria |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 15 |
| Median (95% Confidence Interval) [months] |
7.6
|
| Title | Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1 |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 138 |
| Number [percentage of participants] |
18.8
13.6%
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
204
(47.6)
|
| Day 21 |
933
(34.8)
|
| Title | Time to Cmax (Tmax) of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
5.89
|
| Day 21 |
4.12
|
| Title | Time to Last Measurable Plasma Concentration (Tlast) of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
11.59
(3.9)
|
| Day 21 |
11.65
(3.8)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
1140
(44.5)
|
| Day 21 |
7860
(37.2)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
1340
(44.9)
|
| Day 21 |
9090
(36.9)
|
| Title | Cmax of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
57.2
(68.6)
|
| Day 21 |
303
(33.5)
|
| Title | Tmax of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
8.03
|
| Day 21 |
7.00
|
| Title | Tlast of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
11.59
(3.9)
|
| Day 21 |
11.65
(3.8)
|
| Title | AUC(0-10) of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
300
(68.4)
|
| Day 21 |
2590
(35.0)
|
| Title | AUC(0-last) of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
378
(67.5)
|
| Day 21 |
3040
(34.9)
|
| Title | Metabolite to Parent Ratio Based on AUC(0-10) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
0.278
(41.0)
|
| Day 21 |
0.349
(28.7)
|
| Title | Metabolite to Parent Ratio Based on AUC(0-last) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category. |
| Arm/Group Title | Alectinib |
|---|---|
| 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. |
| Measure Participants | 28 |
| Day 1 |
0.298
(41.2)
|
| Day 21 |
0.354
(28.7)
|
| Title | Trough Plasma Concentration (Ctrough) of Alectinib |
|---|---|
| Description | |
| Time Frame | Pre-dose (0 hrs) on Day 21 of Cycle 1 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 26 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
761
(42.9)
|
| Title | Ctrough of Alectinib Metabolite |
|---|---|
| Description | |
| Time Frame | Pre-dose (0 hrs) on Day 21 of Cycle 1 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 26 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
244
(37.8)
|
| Title | Peak to Trough Ratio of Alectinib |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 26 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.23
(14.4)
|
| Title | Accumulation Ratio of Alectinib |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 26 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
6.95
(42.1)
|
| Title | Accumulation Ratio of Alectinib Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 26 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
8.68
(64.2)
|
Adverse Events
| 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 | |
| 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 (%) | # Events | |
| Total | 75/138 (54.3%) | |
Serious Adverse Events |
||
| Alectinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 39/138 (28.3%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/138 (0.7%) | |
| Cardiac disorders | ||
| Myocardial infarction | 1/138 (0.7%) | |
| Cardiac arrest | 1/138 (0.7%) | |
| Eye disorders | ||
| Retinal detachment | 1/138 (0.7%) | |
| Gastrointestinal disorders | ||
| Constipation | 2/138 (1.4%) | |
| Intestinal perforation | 1/138 (0.7%) | |
| Oesophagitis | 1/138 (0.7%) | |
| Vomiting | 1/138 (0.7%) | |
| Enterovesical fistula | 1/138 (0.7%) | |
| General disorders | ||
| Malaise | 1/138 (0.7%) | |
| Hepatobiliary disorders | ||
| Hyperbilirubinaemia | 3/138 (2.2%) | |
| Cholecystitis | 1/138 (0.7%) | |
| Infections and infestations | ||
| Appendicitis perforated | 1/138 (0.7%) | |
| Intervertebral discitis | 1/138 (0.7%) | |
| Pleural infection | 1/138 (0.7%) | |
| Pneumonia | 2/138 (1.4%) | |
| Sepsis | 1/138 (0.7%) | |
| Appendicitis | 1/138 (0.7%) | |
| Bronchitis | 1/138 (0.7%) | |
| Endocarditis | 1/138 (0.7%) | |
| Enterocolitis infectious | 1/138 (0.7%) | |
| Infection | 1/138 (0.7%) | |
| Influenza | 1/138 (0.7%) | |
| Lower respiratory tract infection | 1/138 (0.7%) | |
| Lung infection | 1/138 (0.7%) | |
| Urosepsis | 1/138 (0.7%) | |
| Injury, poisoning and procedural complications | ||
| Head injury | 1/138 (0.7%) | |
| Ligament rupture | 1/138 (0.7%) | |
| Investigations | ||
| Alanine aminotransferase increased | 2/138 (1.4%) | |
| Aspartate aminotransferase increased | 2/138 (1.4%) | |
| International normalised ratio increased | 1/138 (0.7%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscle haemorrhage | 1/138 (0.7%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Breast cancer | 1/138 (0.7%) | |
| Nervous system disorders | ||
| Seizure | 2/138 (1.4%) | |
| Psychiatric disorders | ||
| Depression | 2/138 (1.4%) | |
| Renal and urinary disorders | ||
| Ureterolithiasis | 1/138 (0.7%) | |
| Reproductive system and breast disorders | ||
| Menorrhagia | 1/138 (0.7%) | |
| Pelvic floor muscle weakness | 1/138 (0.7%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 3/138 (2.2%) | |
| Epistaxis | 1/138 (0.7%) | |
| Haemoptysis | 1/138 (0.7%) | |
| Interstitial lung disease | 1/138 (0.7%) | |
| Pneumothorax | 1/138 (0.7%) | |
| Pulmonary embolism | 3/138 (2.2%) | |
| Pleural effusion | 1/138 (0.7%) | |
| Vascular disorders | ||
| Haemorrhage | 1/138 (0.7%) | |
Other (Not Including Serious) Adverse Events |
||
| Alectinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 133/138 (96.4%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 19/138 (13.8%) | |
| Ear and labyrinth disorders | ||
| Vertigo | 8/138 (5.8%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 11/138 (8%) | |
| Abdominal pain upper | 17/138 (12.3%) | |
| Constipation | 53/138 (38.4%) | |
| Diarrhoea | 27/138 (19.6%) | |
| Nausea | 32/138 (23.2%) | |
| Vomiting | 22/138 (15.9%) | |
| Dyspepsia | 10/138 (7.2%) | |
| General disorders | ||
| Asthenia | 31/138 (22.5%) | |
| Fatigue | 43/138 (31.2%) | |
| Oedema | 9/138 (6.5%) | |
| Oedema peripheral | 42/138 (30.4%) | |
| Pyrexia | 17/138 (12.3%) | |
| Chest pain | 10/138 (7.2%) | |
| Influenza like illness | 8/138 (5.8%) | |
| Infections and infestations | ||
| Upper respiratory tract infection | 21/138 (15.2%) | |
| Bronchitis | 8/138 (5.8%) | |
| Influenza | 7/138 (5.1%) | |
| Sinusitis | 7/138 (5.1%) | |
| Urinary tract infection | 7/138 (5.1%) | |
| Viral upper respiratory tract infection | 15/138 (10.9%) | |
| Investigations | ||
| Alanine aminotransferase increased | 15/138 (10.9%) | |
| Asparatate aminotransferase increased | 18/138 (13%) | |
| Blood bilirubin increased | 18/138 (13%) | |
| Blood creatinine increased | 7/138 (5.1%) | |
| Weight increased | 18/138 (13%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 17/138 (12.3%) | |
| Hypokalaemia | 7/138 (5.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 16/138 (11.6%) | |
| Back pain | 21/138 (15.2%) | |
| Bone pain | 8/138 (5.8%) | |
| Muscular weakness | 11/138 (8%) | |
| Musculoskeletal pain | 14/138 (10.1%) | |
| Myalgia | 36/138 (26.1%) | |
| Pain in extremity | 15/138 (10.9%) | |
| Muscle spasms | 10/138 (7.2%) | |
| Musculoskeletal chest pain | 8/138 (5.8%) | |
| Nervous system disorders | ||
| Dizziness | 16/138 (11.6%) | |
| Headache | 27/138 (19.6%) | |
| Dysgeusia | 7/138 (5.1%) | |
| Paraesthesia | 7/138 (5.1%) | |
| Psychiatric disorders | ||
| Insomnia | 14/138 (10.1%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 32/138 (23.2%) | |
| Dyspnoea | 22/138 (15.9%) | |
| Oropharyngeal pain | 16/138 (11.6%) | |
| Productive cough | 11/138 (8%) | |
| Dysphonia | 7/138 (5.1%) | |
| Nasal congestion | 7/138 (5.1%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 10/138 (7.2%) | |
| Dry skin | 13/138 (9.4%) | |
| Photosensitivity reaction | 16/138 (11.6%) | |
| Rash | 24/138 (17.4%) | |
Limitations/Caveats
Part 1 analysis was not conducted as during the conduct of the study the RP2D was confirmed in study NP28761 (NCT01871805).
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01801111
Other Study ID Numbers:
- NP28673
- 2012-004455-36
First Posted:
Feb 28, 2013
Last Update Posted:
Nov 2, 2018
Last Verified:
Oct 1, 2018