A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases

Study Purpose

The study will compare the efficacy and safety of entrectinib with crizotinib in participants with advanced or metastatic ROS1 non-small cell lung cancer (NSCLC). The participants will self-administer oral entrectinib or crizotinib as described in the protocol and local prescribing information. Treatments will continue until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically or cytologically-confirmed diagnosis of advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors a documented ROS1 gene rearrangement.
  • - No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC.
  • - Prior radiotherapy is allowed if more than 14 days have elapsed between the end of treatment and randomization.
  • - Measurable systemic disease according to RECIST v1.1.
  • - Participants with measurable and non-measurable CNS lesions per RECIST v1.1, including leptomeningeal carcinomatosis.
  • - Life expectancy of at least 12 weeks.
  • - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • - Adequate hematologic, renal, liver functions.
  • - Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment.
  • - Ability to swallow entrectinib and crizotinib intact without chewing, crushing, or opening the capsules.
  • - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the treatment period and for up to 5 weeks after the last dose of entrectinib or for at least 90 days after the last dose of crizotinib.
  • - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

Exclusion Criteria:

  • - Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC.
  • - NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excluding alopecia, fatigue, nausea and lack of appetite), which have not shown improvement and are strictly considered to interfere with current study drug.
  • - History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study.
  • - History of prolonged corrected QTc interval.
  • - Peripheral sensory neuropathy ≥ Grade 2.
  • - Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
  • - Previous malignancy within the past 3 years.
  • - Incomplete recovery from any surgery prior to the start of study treatment.
  • - Active GI disease (e.g., Crohn's disease, ulcerative colitis or short gut syndrome) or other malabsorption syndrome that would reasonably impact drug absorption.
  • - History of prior therapy-induced pneumonitis.
  • - Any condition (in the past 3 months) e.g., myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmias requiring medication.
  • - Known active infections (bacterial, fungal or viral, including human immunodeficiency virus positive) - History of hypersensitivity to any of the additives in the entrectinib and/or crizotinib drug formulations.
  • - Pregnant or lactating women.
  • - Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness.
  • - Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04603807
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hoffmann-La Roche
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Clinical Trials
Principal Investigator Affiliation Hoffmann-La Roche
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Brazil, China, Croatia, France, Germany, Greece, India, Italy, Jordan, Lebanon, Mexico, Netherlands, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand, Turkey
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Carcinoma, Non-Small-Cell Lung
Arms & Interventions

Arms

Experimental: Entrectinib

Participants will be enrolled to receive 600 mg entrectinib orally once daily until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Active Comparator: Crizotinib

Participants will be enrolled to receive 250 mg crizotinib orally twice daily until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.

Interventions

Drug: - Entrectinib

Entrectinib will be self-administered orally at a dose of 600 mg (three 200 mg capsules per day) once daily with or without food.

Drug: - Crizotinib

Crizotinib will be self-administered orally at a dose of 250 mg twice daily with or without food.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Hospital Sao Rafael - HSR, Salvador, Bahia, Brazil

Status

Recruiting

Address

Hospital Sao Rafael - HSR

Salvador, Bahia, 41253-190

Fortaleza, Ceará, Brazil

Status

Recruiting

Address

Oncocentro Serviços Médicos e Hospitalares Ltda

Fortaleza, Ceará, 60130-241

Hospitais Integrados da Gavea S/A, Brasilia, Distrito Federal, Brazil

Status

Active, not recruiting

Address

Hospitais Integrados da Gavea S/A

Brasilia, Distrito Federal, 70390-140

Oncocentro Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil

Status

Withdrawn

Address

Oncocentro Belo Horizonte

Belo Horizonte, Minas Gerais, 30360-680

Ijui, Rio Grande Do Sul, Brazil

Status

Withdrawn

Address

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijui, Rio Grande Do Sul, 98700-000

Florianopolis, Santa Catarina, Brazil

Status

Recruiting

Address

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

Florianopolis, Santa Catarina, 88020-210

Hospital de Cancer de Barretos, Barretos, São Paulo, Brazil

Status

Active, not recruiting

Address

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400

Sao Paulo, São Paulo, Brazil

Status

Active, not recruiting

Address

Instituto do Cancer do Estado de Sao Paulo - ICESP

Sao Paulo, São Paulo, 01246-000

Oncoclinicas Rio de Janeiro S.A., Rio de Janeiro, Brazil

Status

Completed

Address

Oncoclinicas Rio de Janeiro S.A.

Rio de Janeiro, , 22250-905

Beijing Union Hospital, Beijing, China

Status

Withdrawn

Address

Beijing Union Hospital

Beijing, , 100730

Jilin Cancer Hospital, Changchun, China

Status

Active, not recruiting

Address

Jilin Cancer Hospital

Changchun, , 132013

Hunan Cancer Hospital, Changsha City, China

Status

Active, not recruiting

Address

Hunan Cancer Hospital

Changsha City, , 410013

Changsha, China

Status

Active, not recruiting

Address

The Second Xiangya Hospital of Central South University

Changsha, , 410011

West China Hospital, Sichuan University, Chengdu, China

Status

Active, not recruiting

Address

West China Hospital, Sichuan University

Chengdu, , 610041

Guangzhou, China

Status

Active, not recruiting

Address

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, , 510120

Harbin, China

Status

Active, not recruiting

Address

Harbin Medical University Cancer Hospital

Harbin, , 150081

Jining, China

Status

Active, not recruiting

Address

Affiliated Hospital of Jining Medical University

Jining, , 272029

Nanjing City, China

Status

Completed

Address

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing City, , 210008

Nanning, China

Status

Active, not recruiting

Address

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, , 530021

Shanghai Pulmonary Hospital, Shanghai, China

Status

Active, not recruiting

Address

Shanghai Pulmonary Hospital

Shanghai, , 200433

Shiyan, China

Status

Active, not recruiting

Address

Taihe Hospital of Hubei University of Medicine

Shiyan, , 442000

Wuhan City, China

Status

Active, not recruiting

Address

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan City, , 430023

Clinical Hospital Centre Zagreb, Zagreb, Croatia

Status

Recruiting

Address

Clinical Hospital Centre Zagreb

Zagreb, , 10000

Institut Bergonie, Bordeaux, France

Status

Active, not recruiting

Address

Institut Bergonie

Bordeaux, , 33076

CHRU Lille, Lille, France

Status

Active, not recruiting

Address

CHRU Lille

Lille, , 59037

Centre Leon Berard, Lyon, France

Status

Recruiting

Address

Centre Leon Berard

Lyon, , 69008

Hopital Nord AP-HM, Marseille, France

Status

Active, not recruiting

Address

Hopital Nord AP-HM

Marseille, , 13015

CHU Rennes - Hopital Pontchaillou, Rennes cedex 09, France

Status

Recruiting

Address

CHU Rennes - Hopital Pontchaillou

Rennes cedex 09, , 35033

Hopital Larrey, Toulouse, France

Status

Active, not recruiting

Address

Hopital Larrey

Toulouse, , 31059

Hopital Robert Schuman, Vantoux, France

Status

Recruiting

Address

Hopital Robert Schuman

Vantoux, , 57070

Berlin, Germany

Status

Recruiting

Address

HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie

Berlin, , 14165

Gießen, Germany

Status

Recruiting

Address

Universitaetsklinikum Giessen und Marburg GmbH

Gießen, , 35392

Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Status

Recruiting

Address

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , 20246

Kliniken Maria Hilf, Mönchengladbach, Germany

Status

Recruiting

Address

Kliniken Maria Hilf

Mönchengladbach, , 41063

Pius-Hospital, Oldenburg, Germany

Status

Recruiting

Address

Pius-Hospital

Oldenburg, , 26121

Uoa Sotiria Hospital, Athens, Greece

Status

Recruiting

Address

Uoa Sotiria Hospital

Athens, , 115 27

Metropolitan Hospital, Athens, Greece

Status

Recruiting

Address

Metropolitan Hospital

Athens, , 185 47

University Hospital of Larissa, Larissa, Greece

Status

Recruiting

Address

University Hospital of Larissa

Larissa, , 411 10

Thessaloniki, Greece

Status

Recruiting

Address

Euromedical General Clinic of Thessaloniki

Thessaloniki, , 546 45

American Oncology Institute, Hyderabad, Andhra Pradesh, India

Status

Withdrawn

Address

American Oncology Institute

Hyderabad, Andhra Pradesh, 500019

New Delhi, Delhi, India

Status

Recruiting

Address

All India Institute Of Medical Sciences (AIIMS)

New Delhi, Delhi, 110029

MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India

Status

Active, not recruiting

Address

MVR Cancer Centre and Research Institute

Kozhikode, Kerala, 673601

Mumbai, Maharashtra, India

Status

Active, not recruiting

Address

MOC Cancer Care & Research Centre (Unit of Cellcure Cancer Centre Pvt Ltd)

Mumbai, Maharashtra, 400036

Varanasi, Uttar Pradesh, India

Status

Recruiting

Address

Mahamana Pandit Madan Mohan Malaviya Cancer Centre-TMC

Varanasi, Uttar Pradesh, 221005

Tata Medical Center, Kolkata, WEST Bengal, India

Status

Recruiting

Address

Tata Medical Center

Kolkata, WEST Bengal, 700160

Chandigarh, India

Status

Withdrawn

Address

Postgraduate Institute of Medical Education and Research

Chandigarh, , 160012

Napoli, Campania, Italy

Status

Recruiting

Address

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale

Napoli, Campania, 80131

IRCCS Istituto Regina Elena (IFO), Roma, Lazio, Italy

Status

Active, not recruiting

Address

IRCCS Istituto Regina Elena (IFO)

Roma, Lazio, 00144

Roma, Lazio, Italy

Status

Active, not recruiting

Address

Azienda Ospedaliera San Camillo Forlanini

Roma, Lazio, 00152

Genova, Liguria, Italy

Status

Active, not recruiting

Address

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)

Genova, Liguria, 16132

Milano, Lombardia, Italy

Status

Withdrawn

Address

Irccs Istituto Europeo di Oncologia (IEO)

Milano, Lombardia, 20141

Milano, Lombardia, Italy

Status

Recruiting

Address

Asst Grande Ospedale Metropolitano Niguarda

Milano, Lombardia, 20162

Asst Di Monza, Monza, Lombardia, Italy

Status

Withdrawn

Address

Asst Di Monza

Monza, Lombardia, 20900

Orbassano, Piemonte, Italy

Status

Recruiting

Address

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piemonte, 10043

Pisa, Toscana, Italy

Status

Withdrawn

Address

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello

Pisa, Toscana, 56124

IRCCS Istituto Oncologico Veneto (IOV), Padova, Veneto, Italy

Status

Active, not recruiting

Address

IRCCS Istituto Oncologico Veneto (IOV)

Padova, Veneto, 35128

King Hussein Cancer Center, Amman, Jordan

Status

Active, not recruiting

Address

King Hussein Cancer Center

Amman, , 1269

Hotel Dieu de France, Beirut, Lebanon

Status

Recruiting

Address

Hotel Dieu de France

Beirut, ,

Guadalajara, Jalisco, Mexico

Status

Recruiting

Address

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280

Health Pharma Professional Research, Cdmx, Mexico CITY (federal District), Mexico

Status

Active, not recruiting

Address

Health Pharma Professional Research

Cdmx, Mexico CITY (federal District), 03100

SUPERARE, Ciudad de México, Mexico CITY (federal District), Mexico

Status

Withdrawn

Address

SUPERARE

Ciudad de México, Mexico CITY (federal District), 06760

Hospital Universitario, Monterrey, Nuevo LEON, Mexico

Status

Recruiting

Address

Hospital Universitario

Monterrey, Nuevo LEON, 64460

NKI/AvL, Amsterdam, Netherlands

Status

Active, not recruiting

Address

NKI/AvL

Amsterdam, , 1066 CX

UMC St Radboud, Nijmegen, Netherlands

Status

Active, not recruiting

Address

UMC St Radboud

Nijmegen, , 6525 GA

Erasmus MC, Rotterdam, Netherlands

Status

Active, not recruiting

Address

Erasmus MC

Rotterdam, , 3015 GD

Amethyst Cluj, Cluj County, Romania

Status

Recruiting

Address

Amethyst Cluj

Cluj County, , 407280

Cluj Napoca, Romania

Status

Recruiting

Address

Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca

Cluj Napoca, , 400015

Centrul de Oncologie Sfantul Nectarie, Craiova, Romania

Status

Recruiting

Address

Centrul de Oncologie Sfantul Nectarie

Craiova, , 200542

Ploiesti, Romania

Status

Recruiting

Address

Emergency County Clinical Hospital Ploiesti

Ploiesti, ,

Centrul de Oncologie Oncohelp, Timisoara, Romania

Status

Recruiting

Address

Centrul de Oncologie Oncohelp

Timisoara, , 300239

AV Medical Ltd., Sankt-peterburg, Leningrad, Russian Federation

Status

Withdrawn

Address

AV Medical Ltd.

Sankt-peterburg, Leningrad, 199034

Univerzitna nemocnica Bratislava, Bratislava, Slovakia

Status

Recruiting

Address

Univerzitna nemocnica Bratislava

Bratislava, , 826 06

Vychodoslovensky onkologicky ustav, Košice, Slovakia

Status

Withdrawn

Address

Vychodoslovensky onkologicky ustav

Košice, , 040 01

Hospital del Mar, Barcelona, Spain

Status

Active, not recruiting

Address

Hospital del Mar

Barcelona, , 08003

Barcelona, Spain

Status

Active, not recruiting

Address

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , 08908

La Coruna, Spain

Status

Recruiting

Address

Complejo Hospitalario Universitario A Coruña (CHUAC)

La Coruna, , 15006

Hospital Ramon y Cajal, Madrid, Spain

Status

Recruiting

Address

Hospital Ramon y Cajal

Madrid, , 28034

Malaga, Spain

Status

Active, not recruiting

Address

Hospital Regional Universitario Carlos Haya

Malaga, , 29010

Karolinska Universitetssjukhuset, Solna, Stockholm, Sweden

Status

Recruiting

Address

Karolinska Universitetssjukhuset, Solna

Stockholm, , 171 76

Chulalongkorn Hospital, Bangkok, Thailand

Status

Recruiting

Address

Chulalongkorn Hospital

Bangkok, , 10330

Faculty of Med. Siriraj Hosp., Bangkok, Thailand

Status

Recruiting

Address

Faculty of Med. Siriraj Hosp.

Bangkok, , 10700

Prapokklao Hospital, Chanthaburi, Thailand

Status

Recruiting

Address

Prapokklao Hospital

Chanthaburi, , 22000

Songklanagarind Hospital, Songkhla, Thailand

Status

Recruiting

Address

Songklanagarind Hospital

Songkhla, , 90110

Wachira Phayaban, Thailand

Status

Recruiting

Address

Bangkok Metropolitan Administration Medical College and Vajira Hospital

Wachira Phayaban, , 10300

Adana, Turkey

Status

Withdrawn

Address

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, , 01250

Ankara, Turkey

Status

Active, not recruiting

Address

Gazi University Medical Faculty, Oncology Hospital

Ankara, , 06500

Liv Hospital Ankara, Ankara, Turkey

Status

Active, not recruiting

Address

Liv Hospital Ankara

Ankara, , 06680

Ege Uni Medical Faculty Hospital, Izmir, Turkey

Status

Withdrawn

Address

Ege Uni Medical Faculty Hospital

Izmir, , 35100

Malatya, Turkey

Status

Withdrawn

Address

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, , 44280

Ac?badem Maslak Hastanesi Büyükdere, Sar?yer/?stanbul, Turkey

Status

Withdrawn

Address

Ac?badem Maslak Hastanesi Büyükdere

Sar?yer/?stanbul, , 34457

Medical Park Seyhan Hospital, Seyhan, Turkey

Status

Recruiting

Address

Medical Park Seyhan Hospital

Seyhan, , 01140

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