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

NCT ID: NCT04603807

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-30

Study Completion Date

2028-06-26

Brief Summary

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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.

Detailed Description

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Conditions

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Carcinoma, Non-Small-Cell Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Entrectinib

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Crizotinib

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

Crizotinib

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Oncocentro Serviços Médicos e Hospitalares Ltda

Fortaleza, Ceará, Brazil

Site Status RECRUITING

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, Brazil

Site Status RECRUITING

Hospitais Integrados da Gavea S/A

Brasília, Federal District, Brazil

Site Status ACTIVE_NOT_RECRUITING

Oncocentro Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Site Status WITHDRAWN

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, Brazil

Site Status WITHDRAWN

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

Florianópolis, Santa Catarina, Brazil

Site Status RECRUITING

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status ACTIVE_NOT_RECRUITING

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Site Status ACTIVE_NOT_RECRUITING

Oncoclinicas Rio de Janeiro S.A.

Rio de Janeiro, , Brazil

Site Status COMPLETED

Beijing Union Hospital

Beijing, , China

Site Status WITHDRAWN

Jilin Cancer Hospital

Changchun, , China

Site Status ACTIVE_NOT_RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, , China

Site Status ACTIVE_NOT_RECRUITING

Hunan Cancer Hospital

Changsha, , China

Site Status ACTIVE_NOT_RECRUITING

West China Hospital, Sichuan University

Chengdu, , China

Site Status ACTIVE_NOT_RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

Site Status ACTIVE_NOT_RECRUITING

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status ACTIVE_NOT_RECRUITING

Affiliated Hospital of Jining Medical University

Jining, , China

Site Status ACTIVE_NOT_RECRUITING

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

Nanjing, , China

Site Status WITHDRAWN

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, , China

Site Status ACTIVE_NOT_RECRUITING

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status ACTIVE_NOT_RECRUITING

Taihe Hospital of Hubei University of Medicine

Shiyan, , China

Site Status ACTIVE_NOT_RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status ACTIVE_NOT_RECRUITING

Clinical Hospital Centre Zagreb

Zagreb, , Croatia

Site Status RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status ACTIVE_NOT_RECRUITING

CHRU Lille

Lille, , France

Site Status ACTIVE_NOT_RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Hopital Nord AP-HM

Marseille, , France

Site Status ACTIVE_NOT_RECRUITING

CHU Rennes - Hopital Pontchaillou

Rennes, , France

Site Status RECRUITING

Hopital Larrey

Toulouse, , France

Site Status ACTIVE_NOT_RECRUITING

Hopital Robert Schuman

Vantoux, , France

Site Status RECRUITING

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

Berlin, , Germany

Site Status RECRUITING

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, , Germany

Site Status RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Kliniken Maria Hilf

Mönchengladbach, , Germany

Site Status RECRUITING

Pius-Hospital

Oldenburg, , Germany

Site Status RECRUITING

Uoa Sotiria Hospital

Athens, , Greece

Site Status ACTIVE_NOT_RECRUITING

Metropolitan Hospital

Athens, , Greece

Site Status ACTIVE_NOT_RECRUITING

University Hospital of Larissa

Larissa, , Greece

Site Status WITHDRAWN

Euromedical General Clinic of Thessaloniki

Thessaloniki, , Greece

Site Status ACTIVE_NOT_RECRUITING

American Oncology Institute

Hyderabad, Andhra Pradesh, India

Site Status WITHDRAWN

MVR Cancer Centre and Research Institute

Kozhikode, Kerala, India

Site Status COMPLETED

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

Mumbai, Maharashtra, India

Site Status ACTIVE_NOT_RECRUITING

All India Institute Of Medical Sciences (AIIMS)

New Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

Mahamana Pandit Madan Mohan Malaviya Cancer Centre-TMC

Varanasi, Uttar Pradesh, India

Site Status RECRUITING

Tata Medical Center

Kolkata, West Bengal, India

Site Status RECRUITING

Postgraduate Institute of Medical Education and Research

Chandigarh, , India

Site Status WITHDRAWN

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

Napoli, Campania, Italy

Site Status WITHDRAWN

IRCCS Istituto Regina Elena (IFO)

Rome, Lazio, Italy

Site Status WITHDRAWN

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, Italy

Site Status ACTIVE_NOT_RECRUITING

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)

Genoa, Liguria, Italy

Site Status ACTIVE_NOT_RECRUITING

Irccs Istituto Europeo di Oncologia (IEO)

Milan, Lombardy, Italy

Site Status WITHDRAWN

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

Site Status RECRUITING

Asst Di Monza

Monza, Lombardy, Italy

Site Status WITHDRAWN

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piedmont, Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello

Pisa, Tuscany, Italy

Site Status WITHDRAWN

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, Italy

Site Status ACTIVE_NOT_RECRUITING

King Hussein Cancer Center

Amman, , Jordan

Site Status ACTIVE_NOT_RECRUITING

Hotel Dieu de France

Beirut, , Lebanon

Site Status RECRUITING

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Site Status RECRUITING

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

Site Status ACTIVE_NOT_RECRUITING

SUPERARE

Mexico City, Mexico CITY (federal District), Mexico

Site Status WITHDRAWN

Hospital Universitario

Monterrey, Nuevo León, Mexico

Site Status RECRUITING

NKI/AvL

Amsterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

UMC St Radboud

Nijmegen, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Amethyst Cluj

Cluj County, , Romania

Site Status RECRUITING

Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca

Cluj-Napoca, , Romania

Site Status RECRUITING

Centrul de Oncologie Sfantul Nectarie

Craiova, , Romania

Site Status RECRUITING

Emergency County Clinical Hospital Ploiesti

Ploieşti, , Romania

Site Status RECRUITING

Centrul de Oncologie Oncohelp

Timișoara, , Romania

Site Status WITHDRAWN

AV Medical Ltd.

Saint Petersburg, Sankt-Peterburg, Russia

Site Status WITHDRAWN

Univerzitna nemocnica Bratislava

Bratislava, , Slovakia

Site Status RECRUITING

Vychodoslovensky onkologicky ustav

Košice, , Slovakia

Site Status WITHDRAWN

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Site Status ACTIVE_NOT_RECRUITING

Karolinska Universitetssjukhuset, Solna

Stockholm, , Sweden

Site Status RECRUITING

Chulalongkorn Hospital

Bangkok, , Thailand

Site Status RECRUITING

Faculty of Med. Siriraj Hosp.

Bangkok, , Thailand

Site Status RECRUITING

Prapokklao Hospital

Chanthaburi, , Thailand

Site Status RECRUITING

Songklanagarind Hospital

Songkhla, , Thailand

Site Status RECRUITING

Bangkok Metropolitan Administration Medical College and Vajira Hospital

Wachira Phayaban, , Thailand

Site Status RECRUITING

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, , Turkey (Türkiye)

Site Status WITHDRAWN

Gazi University Medical Faculty, Oncology Hospital

Ankara, , Turkey (Türkiye)

Site Status ACTIVE_NOT_RECRUITING

Liv Hospital Ankara

Ankara, , Turkey (Türkiye)

Site Status ACTIVE_NOT_RECRUITING

Ege Uni Medical Faculty Hospital

Izmir, , Turkey (Türkiye)

Site Status WITHDRAWN

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, , Turkey (Türkiye)

Site Status WITHDRAWN

Acıbadem Maslak Hastanesi Büyükdere

Sarıyer/İstanbul, , Turkey (Türkiye)

Site Status WITHDRAWN

Medical Park Seyhan Hospital

Seyhan, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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Brazil China Croatia France Germany Greece India Italy Jordan Lebanon Mexico Netherlands Romania Russia Slovakia Spain Sweden Thailand Turkey (Türkiye)

Central Contacts

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Reference Study ID Number: MO41552 https://forpatients.roche.com/

Role: CONTACT

888-662-6728 (U.S. and Canada)

Other Identifiers

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2019-003859-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-507494-18-00

Identifier Type: CTIS

Identifier Source: secondary_id

MO41552

Identifier Type: -

Identifier Source: org_study_id

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