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

Primary Purpose

Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Alectinib
Docetaxel
Pemetrexed
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)
  • Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib
  • Prior CNS or leptomeningeal metastases allowed if asymptomatic
  • Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study
  • Measurable disease by RECIST Version 1.1 prior to the administration of study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment

Exclusion Criteria:

  • Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix)
  • Participants who have received any previous ALK inhibitor other than crizotinib
  • Any GI disorder that may affect absorption of oral medications

Sites / Locations

  • GHdC Site Notre Dame
  • UZ Antwerpen
  • UZ Gent
  • MBAL Serdika EOOD
  • Centre Francois Baclesse
  • Hopital Bichat Claude Bernard ; Service de Pneumologie
  • Hopital Du Haut Leveque; Service Des Maladies Respiratoires
  • Hopital Foch; Pneumologie
  • Hopital Sainte Musse; Pneumologie
  • Hopital Larrey; Pneumologie
  • Hopital Robert Schuman; Pneumologie
  • Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie
  • Evang. Lungenklinik Berlin Klinik für Pneumologie
  • Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
  • Fachklinik für Lungenerkrankungen
  • Pius-Hospital; Klinik fuer Haematologie und Onkologie
  • Queen Elizabeth Hospital; Clinical Oncology
  • Queen Mary Hospital; Dept. of Clinical Oncology
  • Semmelweis Egyetem X; Pulmonologiai Klinika
  • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
  • AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico
  • Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare
  • Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
  • Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1
  • Irccs Ospedale San Raffaele;Oncologia Medica
  • Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
  • POLICLINICO RODOLICO, U.O. di Oncologia Medica
  • A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii
  • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
  • Chonnam National University Hwasun Hospital
  • Korea University Guro Hospital; Oncology
  • Oslo Universitetssykehus HF; Radiumhospitalet
  • Medical University of Gdansk
  • Hospital Geral; Servico de Pneumologia
  • IPO do Porto; Servico de Oncologia Medica
  • CHVNG/E_Unidade 1; Servico de Pneumologia
  • FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
  • University сlinic of headaches
  • Main Military Clinical Hospital named after N.N. Burdenko
  • City Clinical Oncology Hospital
  • City Clinical Oncology Dispensary
  • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
  • FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU
  • Vychodoslovensky onkologicky ustav
  • Hospital Universitario de Torrejon
  • Hospital de Cruces; Servicio de Oncologia
  • Hospital Universitario La Paz; Servicio de Oncologia
  • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Hospital Universitari i Politecnic La Fe de Valencia
  • Adana Acıbadem Hospital Oncology Department
  • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
  • Istanbul Uni Capa Medical Faculty; Inst. of Oncology
  • Ege University Medical Faculty; Chest Diseases
  • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Alectinib

Premetrexed/Docetaxel

Arm Description

Participants will receive oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.

Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

Secondary Outcome Measures

Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
PFS Using RECIST Version 1.1 as Assessed by IRC
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis.
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.
Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.
Overall Survival (OS)
Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.
Plasma Concentration of Alectinib
Plasma Concentration of Alectinib Metabolite
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
Percentage of Participants With Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Full Information

First Posted
November 11, 2015
Last Updated
October 7, 2019
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02604342
Brief Title
Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib
Official Title
Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase-Positive Advanced Non Small Cell Lung Cancer Patients Previously Treated With Platinum-Based Chemotherapy and Crizotinib
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
November 3, 2015 (Actual)
Primary Completion Date
January 26, 2017 (Actual)
Study Completion Date
August 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alectinib
Arm Type
Experimental
Arm Description
Participants will receive oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Arm Title
Premetrexed/Docetaxel
Arm Type
Active Comparator
Arm Description
Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Intervention Type
Drug
Intervention Name(s)
Alectinib
Intervention Description
Participants will receive oral alectinib at a dose of 600 mg twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere®
Intervention Description
Participants will receive docetaxel at a dose of 75 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
Alimta®
Intervention Description
Participants will receive pemetrexed at a dose of 500 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
Description
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
Time Frame
Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
Secondary Outcome Measure Information:
Title
Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
Description
Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Baseline through study end (up to 33 months)
Title
PFS Using RECIST Version 1.1 as Assessed by IRC
Description
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis.
Time Frame
Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Title
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time Frame
Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Title
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description
Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time Frame
Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Title
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time Frame
From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Title
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Time Frame
Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Title
Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description
Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Time Frame
Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Title
Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description
Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.
Time Frame
From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)
Title
Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Baseline through study end (up to 33 months)
Title
Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
Description
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.
Time Frame
From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Title
Overall Survival (OS)
Description
Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.
Time Frame
Randomization to death from any cause, through study end (up to 33 months)
Title
Plasma Concentration of Alectinib
Time Frame
Predose (2 hours) at Baseline, Week 3 and Week 6
Title
Plasma Concentration of Alectinib Metabolite
Time Frame
Predose (2 hours) at Baseline, Week 3 and Week 6
Title
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Description
Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.
Time Frame
Baseline through Week 138
Title
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Description
Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.
Time Frame
Baseline through Week 138
Title
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Description
Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Time Frame
Baseline through Week 60
Title
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
Description
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time Frame
Baseline through study end (up to 33 months)
Title
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
Description
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time Frame
Baseline through study end (up to 33 months)
Title
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
Description
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time Frame
Baseline through study end (up to 33 months)
Title
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
Description
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time Frame
Baseline through study end (up to 33 months)
Title
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
Description
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
Time Frame
Baseline through study end (up to 33 months)
Title
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
Description
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.
Time Frame
Baseline through study end (up to 33 months)
Title
Percentage of Participants With Adverse Events (AEs)
Description
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame
Baseline through study end (up to 33 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3) Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib Prior CNS or leptomeningeal metastases allowed if asymptomatic Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study Measurable disease by RECIST Version 1.1 prior to the administration of study treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment Exclusion Criteria: Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix) Participants who have received any previous ALK inhibitor other than crizotinib Any GI disorder that may affect absorption of oral medications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
GHdC Site Notre Dame
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
MBAL Serdika EOOD
City
Sofia
ZIP/Postal Code
1632
Country
Bulgaria
Facility Name
Centre Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Hopital Bichat Claude Bernard ; Service de Pneumologie
City
Paris
ZIP/Postal Code
75877
Country
France
Facility Name
Hopital Du Haut Leveque; Service Des Maladies Respiratoires
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
Hopital Foch; Pneumologie
City
Suresnes
ZIP/Postal Code
92151
Country
France
Facility Name
Hopital Sainte Musse; Pneumologie
City
Toulon
ZIP/Postal Code
83056
Country
France
Facility Name
Hopital Larrey; Pneumologie
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hopital Robert Schuman; Pneumologie
City
Vantoux
ZIP/Postal Code
57070
Country
France
Facility Name
Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
Facility Name
Evang. Lungenklinik Berlin Klinik für Pneumologie
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
City
Gauting
ZIP/Postal Code
82131
Country
Germany
Facility Name
Fachklinik für Lungenerkrankungen
City
Immenhausen
ZIP/Postal Code
34376
Country
Germany
Facility Name
Pius-Hospital; Klinik fuer Haematologie und Onkologie
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
Facility Name
Queen Elizabeth Hospital; Clinical Oncology
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Mary Hospital; Dept. of Clinical Oncology
City
Hong Kong
Country
Hong Kong
Facility Name
Semmelweis Egyetem X; Pulmonologiai Klinika
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
City
Avellino
State/Province
Campania
ZIP/Postal Code
83100
Country
Italy
Facility Name
AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
City
Ravenna
State/Province
Emilia-Romagna
ZIP/Postal Code
48100
Country
Italy
Facility Name
Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1
City
Roma
State/Province
Lazio
ZIP/Postal Code
00152
Country
Italy
Facility Name
Irccs Ospedale San Raffaele;Oncologia Medica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20141
Country
Italy
Facility Name
POLICLINICO RODOLICO, U.O. di Oncologia Medica
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95100
Country
Italy
Facility Name
A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
Facility Name
Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
City
Perugia
State/Province
Umbria
ZIP/Postal Code
06156
Country
Italy
Facility Name
Chonnam National University Hwasun Hospital
City
Jeollanam-do
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital; Oncology
City
Seoul
ZIP/Postal Code
152-703
Country
Korea, Republic of
Facility Name
Oslo Universitetssykehus HF; Radiumhospitalet
City
Oslo
ZIP/Postal Code
0310
Country
Norway
Facility Name
Medical University of Gdansk
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Hospital Geral; Servico de Pneumologia
City
Coimbra
ZIP/Postal Code
3041-801
Country
Portugal
Facility Name
IPO do Porto; Servico de Oncologia Medica
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
CHVNG/E_Unidade 1; Servico de Pneumologia
City
Vila Nova De Gaia
ZIP/Postal Code
4434-502
Country
Portugal
Facility Name
FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
City
St Petersburg
State/Province
Leningrad
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
University сlinic of headaches
City
Moscow
State/Province
Moskovskaja Oblast
ZIP/Postal Code
121467
Country
Russian Federation
Facility Name
Main Military Clinical Hospital named after N.N. Burdenko
City
Moscow
ZIP/Postal Code
105229
Country
Russian Federation
Facility Name
City Clinical Oncology Hospital
City
Moscow
ZIP/Postal Code
143423
Country
Russian Federation
Facility Name
City Clinical Oncology Dispensary
City
Saint-Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
City
Saint-Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU
City
Banska Bystrica
ZIP/Postal Code
975 17
Country
Slovakia
Facility Name
Vychodoslovensky onkologicky ustav
City
Košice
ZIP/Postal Code
040 01
Country
Slovakia
Facility Name
Hospital Universitario de Torrejon
City
Torrejon de Ardoz
State/Province
Madrid
ZIP/Postal Code
28850
Country
Spain
Facility Name
Hospital de Cruces; Servicio de Oncologia
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital Universitario La Paz; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Adana Acıbadem Hospital Oncology Department
City
Adana
ZIP/Postal Code
01130
Country
Turkey
Facility Name
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Istanbul Uni Capa Medical Faculty; Inst. of Oncology
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Ege University Medical Faculty; Chest Diseases
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
City
Malatya
ZIP/Postal Code
44280
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
29668860
Citation
Novello S, Mazieres J, Oh IJ, de Castro J, Migliorino MR, Helland A, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. doi: 10.1093/annonc/mdy121.
Results Reference
derived

Learn more about this trial

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

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