A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT01871805
• Recruitment Status: Completed
• First Posted: June 7, 2013
• Results First Posted: February 12, 2016
• Last Update Posted: August 21, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Alectinib	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 134 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of the ALK Inhibitor CH5424802/ RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Crizotinib
• Actual Study Start Date: September 30, 2013
• Actual Primary Completion Date: October 24, 2014
• Actual Study Completion Date: August 31, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Alectinib: Phase I (Dose Escalation); Participants will receive escalating doses of alectinib capsules orally until disease progression, death or withdrawal for any other reasons.	Drug: Alectinib; Participants will receive alectinib as described in the arm descriptions.; Other Names: CH5424802; RO5424802
Experimental: Alectinib (Phase II: RP2 dose); Participants will receive recommended Phase II dose as determined from Phase I until disease progression, death or withdrawal for any other reasons.	Drug: Alectinib; Participants will receive alectinib as described in the arm descriptions.; Other Names: CH5424802; RO5424802

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Dose Limiting Toxicities (DLTs): Phase I [ Time Frame: Throughout Cycle 1 of Phase I (21 days) ]
   The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of >=7 days which the Investigator could not rule out as been related to alectinib.
2. Recommended Phase II Dose (RP2D): Phase I [ Time Frame: Throughout Cycle 1 of Phase I (21 days) ]
   RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.
3. Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II [ Time Frame: Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days) ]
   Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).

Secondary Outcome Measures :

1. Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
2. Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
3. Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI.
4. Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   Disease control rate assessed according to RECIST v1.1 was defined as the percentage of participants with a best overall response of CR, PR, or stable disease (SD) lasting for at least 12 weeks, after the first dose of alectinib. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. 95% CI for rate was constructed using Clopper-Pearson method.
5. Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   Percentage of participants with disease progression according to RECIST v1.1 by IRC is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
6. Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
7. Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   Percentage of participants with disease progression according to RECIST v1.1 by investigator is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
8. PFS According to RECIST v1.1 by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
   PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
9. Percentage of Participants Who Died Due to Any Cause: Phase II [ Time Frame: Baseline up to death (any cause) (maximum follow up 284 weeks) ]
10. Overall Survival (OS) Time: Phase II [ Time Frame: Baseline up to death (any cause) (maximum follow up 284 weeks) ]
    OS was defined as the time between date of first dose and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants without any follow-up information were censored at the date of first dose. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
11. DOR According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
12. DOR According to RECIST v1.1 by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
13. Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    COR rate (CORR) was defined as the percentage of participants who had a CR or PR of the baseline central nervous system (CNS) lesions, based on RECIST v.1.1. CNS responses according to RECIST v1.1 did not have to be confirmed. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). 95% CI was computed using the Clopper-Pearson method.
14. Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    CORR was defined as the percentage of participants who had a CR or PR according to RANO criteria of the baseline CNS lesions. As per RANO criteria, CR was defined as disappearance of all enhancing measurable and non-measurable disease, and no new lesions along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and stable or improved non enhancing T2/FLAIR lesions; PR was defined as 50% or more decrease in sum of the products of the diameters (SPD) of measurable enhancing measurable lesions, no new lesion along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and no progression of non-measurable disease (enhancing and non-enhancing T2/FLAIR lesions. Clopper-Pearson method was used to calculate 95% CI.
15. CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    CDOR was defined for CNS responders as the time from the first observation of a CNS response of CR or PR until first observation of CNS progression or death from any cause. An analysis by IRC using RECIST v1.1 was performed. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
16. CDOR According to RANO Criteria by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    CDOR was defined as the time from the first observation of a CNS response of CR or PR according to RANO criteria until first observation of CNS progression or death from any cause. An analysis by RANO criteria was performed. Definitions of CR or PR as per RANO was included in description of Outcome Measure 17. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease) and clear worsening of neurological status with respect to the previous timepoint. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
17. Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RECIST v1.1. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
18. Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days) ]
    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RANO criteria. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).
19. Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days) ]
20. Cmax After Multiple Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days) ]
21. Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days) ]
    AUCinf = AUC from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0- t) plus AUC (t-inf).
22. AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days) ]
23. Ctrough After Multiple Dose of Alectinib: Phase II [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days) ]
24. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II [ Time Frame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks) ]
    EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to lie between 0-100 scale; for each of the symptom scales, higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below (e.g. Global health status/QoL [quality of life]) represents absolute data at baseline. QoL=quality of life
25. Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II [ Time Frame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks) ]
    EORTC QLQ-LC13 consisted of 13 questions for dyspnea (3 items) and 10 single items (cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain). Questions used 4-point scale (1 'Not at all' to 4 'Very much'). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below represents absolute data at baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC
• ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test
• NSCLC that has failed crizotinib treatment
• Measurable disease as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2
• Adequate hematologic, hepatic and renal function

Exclusion Criteria:

• Prior therapy with ALK inhibitor other than crizotinib
• Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment
• History of serious cardiac dysfunction
• History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
• Clinically significant gastrointestinal abnormality that would affect absorption of the drug
• Pregnant or lactating women

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, California

University of California Irvine

Irvine, California, United States, 92697

UCSD Moores Cancer Center

La Jolla, California, United States, 92093

Loma Linda Cancer Center

Loma Linda, California, United States, 92354

UCLA

Los Angeles, California, United States, 90095

United States, Colorado

Univ of Colorado Canc Ctr

Aurora, Colorado, United States, 80045

National Jewish Health

Denver, Colorado, United States, 80206

United States, Florida

Lynn Regional Cancer Center West

Boca Raton, Florida, United States, 33486

Florida Hospital Cancer Inst

Orlando, Florida, United States, 32804

UF Health Orlando

Orlando, Florida, United States, 32806

H. Lee Moffitt Cancer Center and Research Inst.

Tampa, Florida, United States, 33612

United States, Illinois

University of Illinois Cancer Center

Chicago, Illinois, United States, 60612

Monroe Medical Associates; Ingalls Memorial Hosp

Harvey, Illinois, United States, 60426

United States, Massachusetts

Massachussets General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Dana Farber Can Ins

Boston, Massachusetts, United States, 02215

Newton-Wellesley Hospital

Newton, Massachusetts, United States, 02462

United States, Michigan

St. Joseph Mercy Hospital; Cancer Care Center.

Ann Arbor, Michigan, United States, 48106

Wayne State Uni ; Karmanos Cancer Center

Detroit, Michigan, United States, 48201

United States, New Jersey

Hackensack Univ Med Ctr

Hackensack, New Jersey, United States, 07601

United States, New York

Roswell Park Cancer Inst.

Buffalo, New York, United States, 14263

Memorial Sloan-Kettering Cancer Center

Commack, New York, United States, 11725

Richmond University Medical Center; Pharmacy Department

Staten Island, New York, United States, 10310

United States, North Carolina

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

United States, Oregon

Providence Portland Med Ctr

Portland, Oregon, United States, 97213

Oregon Health & Science Uni

Portland, Oregon, United States, 97239

United States, Pennsylvania

St. Luke's Hospital; Pharmacy Department

Bethlehem, Pennsylvania, United States, 18015

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, United States, 17033

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

University of Pittsburgh Cancer Pavillion

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

MUSC Hollings Cancer Center

Charleston, South Carolina, United States, 29425

United States, Tennessee

Center for Biomedical Research LLC

Knoxville, Tennessee, United States, 37909

United States, Texas

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States, 75246

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Virginia

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

United States, Washington

Swedish Cancer Inst.

Seattle, Washington, United States, 98104

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada, L1G 2B9

Canada, Quebec

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada, H3T 1E2

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gadgeel S, Shaw AT, Barlesi F, Crino L, Yang JC, Dingemans AM, Kim DW, de Marinis F, Schulz M, Liu S, Gupta R, Smoljanovic V, Ou SI. Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies. Lung Cancer (Auckl). 2019 Nov 13;10:125-130. doi: 10.2147/LCTT.S209231. eCollection 2019.

Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Lena H, Popat S, Ahn JS, Dansin E, Mitry E, Muller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. doi: 10.1016/j.lungcan.2019.10.015. Epub 2019 Oct 14.

Morcos PN, Nueesch E, Jaminion F, Guerini E, Hsu JC, Bordogna W, Balas B, Mercier F. Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 2018 Jul;82(1):129-138. doi: 10.1007/s00280-018-3597-5. Epub 2018 May 10.

Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Dec;34(34):4079-4085. doi: 10.1200/JCO.2016.68.4639. Epub 2016 Oct 31. Erratum In: J Clin Oncol. 2017 May 10;35(14):1631.

Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.

Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SI; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-242. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. Erratum In: Lancet Oncol. 2017 Mar;18(3):e134.

Gadgeel SM, Gandhi L, Riely GJ, Chiappori AA, West HL, Azada MC, Morcos PN, Lee RM, Garcia L, Yu L, Boisserie F, Di Laurenzio L, Golding S, Sato J, Yokoyama S, Tanaka T, Ou SH. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014 Sep;15(10):1119-28. doi: 10.1016/S1470-2045(14)70362-6. Epub 2014 Aug 18.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01871805
• Obsolete Identifiers: NCT01588028
• Other Study ID Numbers: NP28761
• First Posted: June 7, 2013
• Results First Posted: February 12, 2016
• Last Update Posted: August 21, 2018
• Last Verified: July 2018

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Alectinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action