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

Non-Small-Cell Lung Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01801111
• Other study ID #: NP28673
• Secondary ID: 2012-004455-36
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 20, 2013
• Est. completion date: October 27, 2017

Study information

• Verified date: October 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: October 27, 2017
• Est. primary completion date: October 24, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Carcinoma

Intervention

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.
• Alectinib
Alectinib will be administered at a dose of 600 milligrams (mg) via capsule, orally, twice daily.

Locations

Country	Name	City	State
Australia	Prince Charles Hospital	Chermside	Queensland
Australia	Townsville General Hospital	Douglas	Queensland
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	AZ Delta (Campus Wilgenstraat)	Roeselare
Denmark	University Hospital Herlev	Herlev
France	CHU Angers - Hôpital Hôtel Dieu	Angers
France	Hopital Morvan	Brest
France	Centre Francois Baclesse	Caen
France	Centre Georges François Leclerc; Service Pharmacie, Bp 77980	Dijon
France	CHU de Grenoble - Hôpital Nord; Service d'Oncologie Thoracique	Grenoble
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Hôpital Nord - AP-HM Marseille#; Gastroenterology and Hepatology	Marseille cedex 20
France	Groupe Hospitalier Sud - Hôpital Haut Lévêque	Pessac
France	Hopital Pontchaillou - CHU de Rennes	Rennes
France	ICO Rene Gauducheau; CEC	St Herblain
France	Nouvel Hopital Civil - CHU Strasbourg	Strasbourg
France	CHU de Toulouse - Hôpital Larrey	Toulouse
Germany	Charité Campus Virchow-Klinikum; Department of Cardiology	Berlin
Germany	Diakonie Kaiserswerth; Florence-Nightingale-Krankenhaus	Düsseldorf
Germany	LungenClinic Großhansdorf	Großhansdorf
Germany	Lungenklinik Hemer	Hemer
Germany	Klinikum Koeln-Merheim	Koeln
Germany	Mathias-Spital Rheine	Rheine
Italy	Irccs Centro Di Riferimento Oncologico (CRO)	Aviano	Friuli-Venezia Giulia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	Ospedale Versilia	Lido Di Camaiore	Toscana
Italy	Presidio Ospedaliero Campo di Marte	Lucca	Toscana
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	A.O. Universitaria Di Parma	Parma	Emilia-Romagna
Italy	Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia	Perugia	Umbria
Italy	AO San Camillo Forlanini	Roma	Lazio
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma	Lazio
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System; Pharmacy	Seoul
Luxembourg	Centre Hospitalier de Luxembourg	Luxembourg
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Maastricht University Medical Centre; Afdeling Klinische Farmacie en Toxicologie	Maastricht
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement	Moskva	Moskovskaja Oblast
Singapore	Johns Hopkins Singapore	Singapore
Singapore	National University Hospital; Investigational Medicine Unit	Singapore
Spain	Hospital General Univ. de Alicante	Alicante
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Quiron Dexeus	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hosp Clinico Univ Lozano Blesa	Zaragoza
Sweden	Karolinska	Stockholm
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	Royal Marsden Hospital;Dept of Haematology Oncology Research	London
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Rush University Medical Center	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Advanced Medical Specialties	Miami	Florida
United States	Columbia University Medical Center; Department of Hematology/Oncology	New York	New York
United States	UC Irvine Medical Center	Orange	California
United States	Florida Hospital Cancer Inst	Orlando	Florida
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	UCLA Cancer Center; Premiere Oncology, A Medical Corporation	Santa Monica	California
United States	Midwestern Regional Medical Center; Office of Research	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Italy,  Korea, Republic of,  Luxembourg,  Netherlands,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase 2 Dose (RP2D) of Alectinib	RP2D was to be determined based on the safety and tolerability profile of the study treatment.	Cycle 1 (up to 28 days)
Primary	Percentage of Participants With Dose Limiting Toxicities (DLTs)	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.	Cycle 1 (up to 28 days)
Primary	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	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.	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)
Primary	Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants	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.	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)
Secondary	Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants	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).	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)
Secondary	Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population	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.	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)
Secondary	Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants	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).	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)
Secondary	Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants	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).	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)
Secondary	Duration of Response (DoR) as Assessed by IRC in RE Population	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.	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)
Secondary	Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population	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.	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)
Secondary	Progression Free Survival (PFS) as Assessed by IRC in Safety Population	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.	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)
Secondary	Percentage of Participants Who Died of Any Cause	Percentage of participants who died of any cause was reported.	Baseline up to death from any cause (up to approximately 4 years)
Secondary	Overall Survival (OS)	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.	Baseline up to death from any cause (up to approximately 4 years)
Secondary	Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population	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.	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)
Secondary	Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1	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.	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)
Secondary	Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria	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.	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)
Secondary	CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1	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.	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)
Secondary	CDoR as Assessed by IRC According to RANO Criteria	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.	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)
Secondary	Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1	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.	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)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Alectinib	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.	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
Secondary	Time to Cmax (Tmax) of Alectinib	Tmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.	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
Secondary	Time to Last Measurable Plasma Concentration (Tlast) of Alectinib	Tlast for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.	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
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib	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).	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
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib	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).	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
Secondary	Cmax of Alectinib Metabolite	Cmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.	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
Secondary	Tmax of Alectinib Metabolite	Tmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.	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
Secondary	Tlast of Alectinib Metabolite	Tlast for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.	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
Secondary	AUC(0-10) of Alectinib Metabolite	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).	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
Secondary	AUC(0-last) of Alectinib Metabolite	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).	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
Secondary	Metabolite to Parent Ratio Based on AUC(0-10)	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.	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
Secondary	Metabolite to Parent Ratio Based on AUC(0-last)	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.	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
Secondary	Trough Plasma Concentration (Ctrough) of Alectinib		Pre-dose (0 hrs) on Day 21 of Cycle 1
Secondary	Ctrough of Alectinib Metabolite		Pre-dose (0 hrs) on Day 21 of Cycle 1
Secondary	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
Secondary	Accumulation Ratio of Alectinib	Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.	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
Secondary	Accumulation Ratio of Alectinib Metabolite	Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.	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