Clinical trial NCT02604342: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-13
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
timeFrame: Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
Secondary outcomes:
measure: Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
timeFrame: Baseline through study end (up to 33 months)
measure: PFS Using RECIST Version 1.1 as Assessed by IRC
timeFrame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
measure: Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
timeFrame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
measure: Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
timeFrame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
measure: Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
timeFrame: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
measure: PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
timeFrame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
measure: Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
timeFrame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
measure: Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
timeFrame: From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)
measure: Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
timeFrame: Baseline through study end (up to 33 months)
measure: Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
timeFrame: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause, through study end (up to 33 months)
measure: Plasma Concentration of Alectinib
timeFrame: Predose (2 hours) at Baseline, Week 3 and Week 6
measure: Plasma Concentration of Alectinib Metabolite
timeFrame: Predose (2 hours) at Baseline, Week 3 and Week 6
measure: Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
timeFrame: Baseline through Week 138
measure: Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
timeFrame: Baseline through Week 138
measure: Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
timeFrame: Baseline through Week 60
measure: Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
timeFrame: Baseline through study end (up to 33 months)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline through study end (up to 33 months)
Other outcomes:
Locations:
city: Charleroi
country: Belgium
facility: GHdC Site Notre Dame
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Sofia
country: Bulgaria
facility: MBAL Serdika EOOD
city: Caen
country: France
facility: Centre Francois Baclesse
city: Paris
country: France
facility: Hopital Bichat Claude Bernard ; Service de Pneumologie
city: Pessac
country: France
facility: Hopital Du Haut Leveque; Service Des Maladies Respiratoires
city: Suresnes
country: France
facility: Hopital Foch; Pneumologie
city: Toulon
country: France
facility: Hopital Sainte Musse; Pneumologie
city: Toulouse
country: France
facility: Hopital Larrey; Pneumologie
city: Vantoux
country: France
facility: Hopital Robert Schuman; Pneumologie
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie
city: Berlin
country: Germany
facility: Evang. Lungenklinik Berlin Klinik für Pneumologie
city: Gauting
country: Germany
facility: Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Oldenburg
country: Germany
facility: Pius-Hospital; Klinik fuer Haematologie und Onkologie
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital; Clinical Oncology
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Dept. of Clinical Oncology
city: Budapest
country: Hungary
facility: Semmelweis Egyetem X; Pulmonologiai Klinika
city: Avellino
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
state: Campania
city: Napoli
country: Italy
facility: AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico
state: Campania
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare
state: Campania
city: Ravenna
country: Italy
facility: Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1
state: Lazio
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
state: Lombardia
city: Catania
country: Italy
facility: POLICLINICO RODOLICO, U.O. di Oncologia Medica
state: Sicilia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii
state: Toscana
city: Perugia
country: Italy
facility: Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
state: Umbria
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital; Oncology
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF; Radiumhospitalet
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Coimbra
country: Portugal
facility: Hospital Geral; Servico de Pneumologia
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Vila Nova De Gaia
country: Portugal
facility: CHVNG/E_Unidade 1; Servico de Pneumologia
city: St Petersburg
country: Russian Federation
facility: FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
state: Leningrad
city: Moscow
country: Russian Federation
facility: University сlinic of headaches
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Main Military Clinical Hospital named after N.N. Burdenko
city: Moscow
country: Russian Federation
facility: City Clinical Oncology Hospital
city: Saint-Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
city: Banska Bystrica
country: Slovakia
facility: FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU
city: Košice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav
city: Torrejon de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Bilbao
country: Spain
facility: Hospital de Cruces; Servicio de Oncologia
state: Vizcaya
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Adana
country: Turkey
facility: Adana Acıbadem Hospital Oncology Department
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Istanbul
country: Turkey
facility: Istanbul Uni Capa Medical Faculty; Inst. of Oncology
city: Izmir
country: Turkey
facility: Ege University Medical Faculty; Chest Diseases
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.