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

NCT02604342 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: MO297502015-000634-29
• Study Type: interventional
• Target: 119
• Locations: 15 countries
• Sites: 54

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).

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)

Secondary Outcomes (23)

• Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC

  Baseline through study end (up to 33 months)

• PFS Using RECIST Version 1.1 as Assessed by IRC

  Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

• Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC

  Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

• Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC

  Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

• Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC

  From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)

Study Arms (2)

Alectinib

EXPERIMENTAL

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.

Drug: Alectinib

Premetrexed/Docetaxel

ACTIVE COMPARATOR

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.

Drug: Docetaxel; Drug: Pemetrexed

Interventions

Alectinib DRUG

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.

Alectinib

Docetaxel DRUG

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.

Also known as: Taxotere®

Premetrexed/Docetaxel

Pemetrexed DRUG

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.

Also known as: Alimta®

Premetrexed/Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (54)

GHdC Site Notre Dame

Charleroi, 6000, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

MBAL Serdika EOOD

Sofia, 1632, Bulgaria

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Hopital Bichat Claude Bernard ; Service de Pneumologie

Paris, 75877, France

Location

Hopital Du Haut Leveque; Service Des Maladies Respiratoires

Pessac, 33600, France

Location

Hopital Foch; Pneumologie

Suresnes, 92151, France

Location

Hopital Sainte Musse; Pneumologie

Toulon, 83056, France

Location

Hopital Larrey; Pneumologie

Toulouse, 31059, France

Location

Hopital Robert Schuman; Pneumologie

Vantoux, 57070, France

Location

Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie

Bad Berka, 99437, Germany

Location

Evang. Lungenklinik Berlin Klinik für Pneumologie

Berlin, 13125, Germany

Location

Asklepios-Fachkliniken Muenchen-Gauting; Onkologie

Gauting, 82131, Germany

Location

Fachklinik für Lungenerkrankungen

Immenhausen, 34376, Germany

Location

Pius-Hospital; Klinik fuer Haematologie und Onkologie

Oldenburg, 26121, Germany

Location

Queen Elizabeth Hospital; Clinical Oncology

Hong Kong, Hong Kong

Location

Queen Mary Hospital; Dept. of Clinical Oncology

Hong Kong, Hong Kong

Location

Semmelweis Egyetem X; Pulmonologiai Klinika

Budapest, 1083, Hungary

Location

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati

Avellino, Campania, 83100, Italy

Location

AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico

Napoli, Campania, 80131, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare

Napoli, Campania, 80131, Italy

Location

Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica

Ravenna, Emilia-Romagna, 48100, Italy

Location

Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1

Rome, Lazio, 00152, Italy

Location

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, 20132, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milan, Lombardy, 20141, Italy

Location

POLICLINICO RODOLICO, U.O. di Oncologia Medica

Catania, Sicily, 95100, Italy

Location

A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii

Pisa, Tuscany, 56124, Italy

Location

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Perugia, Umbria, 06156, Italy

Location

Oslo Universitetssykehus HF; Radiumhospitalet

Oslo, 0310, Norway

Location

Medical University of Gdansk

Gdansk, 80-952, Poland

Location

Hospital Geral; Servico de Pneumologia

Coimbra, 3041-801, Portugal

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

CHVNG/E_Unidade 1; Servico de Pneumologia

Vila Nova de Gaia, 4434-502, Portugal

Location

University сlinic of headaches

Moscow, Moscow Oblast, 121467, Russia

Location

FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Main Military Clinical Hospital named after N.N. Burdenko

Moscow, 105229, Russia

Location

City Clinical Oncology Hospital

Moscow, 143423, Russia

Location

City Clinical Oncology Dispensary

Saint Petersburg, 197022, Russia

Location

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

Saint Petersburg, 197758, Russia

Location

FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU

Banská Bystrica, 975 17, Slovakia

Location

Vychodoslovensky onkologicky ustav

Košice, 040 01, Slovakia

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Korea University Guro Hospital; Oncology

Seoul, 152-703, South Korea

Location

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid, 28850, Spain

Location

Hospital de Cruces; Servicio de Oncologia

Bilbao, Vizcaya, 48903, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, 29010, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Adana Acıbadem Hospital Oncology Department

Adana, 01130, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Ankara, 06100, Turkey (Türkiye)

Location

Istanbul Uni Capa Medical Faculty; Inst. of Oncology

Istanbul, 34093, Turkey (Türkiye)

Location

Ege University Medical Faculty; Chest Diseases

Izmir, 35040, Turkey (Türkiye)

Location

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, 44280, Turkey (Türkiye)

Location

Related Publications (2)

• Sikkema BJ, Baart SJ, Paats MS, Smit EF, Schols AMWJ, Mathijssen RHJ, van Rossum EFC, Dingemans AC. Body Weight Gain Associated With Alectinib in Patients With ALK+ Non-Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials. J Clin Oncol. 2025 Feb 20;43(6):641-650. doi: 10.1200/JCO-24-01579. Epub 2024 Dec 11.

  PMID: 39661917 DERIVED

• 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.

  PMID: 29668860 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib; Docetaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: November 13, 2015
• Study Start: November 3, 2015
• Primary Completion: January 26, 2017
• Study Completion: August 13, 2018
• Last Updated: October 29, 2019
• Results First Posted: February 26, 2018

Record last verified: 2019-10

Locations

NO (1); PL (1); IT (10); BE (3); DE (5); SL (2); KR (2); BU (1); FR (7); PT (3); RU (6); ES (5); HK (2); HU (1); TU (5)