Clinical trial NCT04603807: 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
Official title: Randomized, Open Label, Multicenter, Phase III Study of Entrectinib Versus Crizotinib in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring ROS1 Gene Rearrangements With and Without Central Nervous System Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: ROS1 Non-small-cell lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-27
Enrollment: 220
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: 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.


Eligibility 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.

Primary outcomes:
measure: Progression-free survival (PFS) in participants with central nervous system (CNS) metastases at baseline
timeFrame: Up to 7 years
Secondary outcomes:
measure: Progression-free survival in the Central Nervous System (CNS-PFS)
timeFrame: Up to 7 Years
measure: Overall response rate (ORR)
timeFrame: Up to 7 Years
measure: Duration of response (DOR)
timeFrame: Up to 7 Years
measure: Progression-free survival (PFS)
timeFrame: Up to 7 years
measure: Overall survival (OS)
timeFrame: Up to 7 Years
measure: Percentage of participants with confirmed deterioration as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
timeFrame: Up to 7 Years
measure: Percentage of participants with impact on lung cancer-specific symptoms assessed by the EORTC QLQ-LC13
timeFrame: Up to 7 Years
measure: Objective response rate in the CNS-ORR in participants with CNS metastases at baseline
timeFrame: Up to 7 Years
measure: Duration of response in the CNS (CNS-DOR) in participants with CNS metastases at baseline
timeFrame: Up to 7 Years
measure: Percentage of participants with Adverse Events and Serious Adverse Events and Adverse Events leading to dose modifications/interruptions, study drug withdrawal or death
timeFrame: Up to 7 Years
Other outcomes:
measure: Change in the scores of EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L)
timeFrame: Up to 7 Years
Locations:
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Fortaleza
country: Brazil
facility: Oncocentro Serviços Médicos e Hospitalares Ltda
state: Ceará
city: Brasilia
country: Brazil
facility: Hospitais Integrados da Gavea S/A
state: Distrito Federal
city: Belo Horizonte
country: Brazil
facility: Oncocentro Belo Horizonte
state: Minas Gerais
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: Florianopolis
country: Brazil
facility: Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro S.A.
city: Beijing
country: China
facility: Beijing Union Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
city: Nanjing City
country: China
facility: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
city: Nanning
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Shiyan
country: China
facility: Taihe Hospital of Hubei University of Medicine
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Toulouse
country: France
facility: Hopital Larrey
city: Vantoux
country: France
facility: Hopital Robert Schuman
city: Berlin
country: Germany
facility: HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie
city: Gießen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf
city: Oldenburg
country: Germany
facility: Pius-Hospital
city: Athens
country: Greece
facility: Uoa Sotiria Hospital
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Larissa
country: Greece
facility: University Hospital of Larissa
city: Thessaloniki
country: Greece
facility: Euromedical General Clinic of Thessaloniki
city: Hyderabad
country: India
facility: American Oncology Institute
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institute Of Medical Sciences (AIIMS)
state: Delhi
city: Kozhikode
country: India
facility: MVR Cancer Centre and Research Institute
state: Kerala
city: Mumbai
country: India
facility: MOC Cancer Care & Research Centre (Unit of Cellcure Cancer Centre Pvt Ltd)
state: Maharashtra
city: Varanasi
country: India
facility: Mahamana Pandit Madan Mohan Malaviya Cancer Centre-TMC
state: Uttar Pradesh
city: Kolkata
country: India
facility: Tata Medical Center
state: WEST Bengal
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
state: Campania
city: Roma
country: Italy
facility: IRCCS Istituto Regina Elena (IFO)
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)
state: Liguria
city: Milano
country: Italy
facility: Irccs Istituto Europeo di Oncologia (IEO)
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Monza
country: Italy
facility: Asst Di Monza
state: Lombardia
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga
state: Piemonte
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: Beirut
country: Lebanon
facility: Hotel Dieu de France
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
state: Jalisco
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Ciudad de México
country: Mexico
facility: SUPERARE
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario
state: Nuevo LEON
city: Amsterdam
country: Netherlands
facility: NKI/AvL
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Cluj County
country: Romania
facility: Amethyst Cluj
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantul Nectarie
city: Ploiesti
country: Romania
facility: Emergency County Clinical Hospital Ploiesti
city: Timisoara
country: Romania
facility: Centrul de Oncologie Oncohelp
city: Sankt-peterburg
country: Russian Federation
facility: AV Medical Ltd.
state: Leningrad
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
city: Košice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Wachira Phayaban
country: Thailand
facility: Bangkok Metropolitan Administration Medical College and Vajira Hospital
city: Adana
country: Turkey
facility: Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty, Oncology Hospital
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
city: Sar?yer/?stanbul
country: Turkey
facility: Ac?badem Maslak Hastanesi Büyükdere
city: Seyhan
country: Turkey
facility: Medical Park Seyhan Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: