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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04603807
• Other study ID #: MO41552
• Secondary ID: 2019-003859-11
• Status: Recruiting
• Phase: Phase 3
• Start date: September 30, 2021
• Est. completion date: December 1, 2027

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: MO41552 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: December 1, 2027
• Est. primary completion date: December 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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

Locations

Country	Name	City	State
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospitais Integrados da Gavea S/A	Brasilia	DF
Brazil	YNOVA Pesquisa Clinica	Florianopolis	SC
Brazil	Oncoclinicas Rio de Janeiro S.A.	Rio de Janeiro	RJ
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
China	Beijing Union Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	The Second Xiangya Hospital of Central South University	Changsha
China	Hunan Cancer Hospital	Changsha CITY
China	Sichuan Provincial Cancer Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Affiliated Hospital of Jining Medical University	Jining
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Shanghai Pulmonary Hospital	Shanghai
China	Taihe Hospital of Hubei University of Medicine	Shiyan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
Croatia	Clinical Hospital Centre Zagreb	Zagreb
France	Institut Bergonie; Pneumology	Bordeaux
France	CHRU Lille	Lille
France	Centre Leon Berard	Lyon
France	Hopital Nord AP-HM	Marseille
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09
France	Hopital Larrey; Pneumologie	Toulouse
France	Hopital Robert Schuman; Pneumologie	Vantoux
Greece	Metropolitan Hospital	Athens
Greece	Uoa Sotiria Hospital; Oncology	Athens
Greece	University Hospital of Larissa;Department of Medical Oncology	Larissa
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
India	Postgraduate Institute of Medical Education and Research	Chandigarh
India	American Oncology Institute	Hyderabad	Andhra Pradesh
India	Tata Medical Center; Department of Medical Oncology	Kolkata	WEST Bengal
India	MVR Cancer Centre and Research Institute	Kozhikode	Kerala
India	MOC Cancer Care & Research Centre	Mumbai	Maharashtra
India	MOC Cancer Care & Research Centre (Unit of Cellcure Cancer Centre Pvt Ltd)	Mumbai	Maharashtra
India	All India Institute Of Medical Sciences (AIIMS)	New Delhi	Delhi
India	Christian Medical College	Ranipet	Tamil NADU
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	ASST DI MONZA; Oncologia Medica	Monza	Lombardia
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga; SSD Oncologia Polomonare (II PAD. IV PIANO)	Orbassano	Piemonte
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana
Italy	Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio
Italy	IRCCS Istituto Regina Elena (IFO); Oncologia Medica B	Roma	Lazio
Jordan	King Hussein Cancer Center	Amman
Lebanon	Hotel Dieu de France	Beirut
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Superare; Centro de Infusion	Ciudad de México	Mexico CITY (federal District)
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Hospital Universitario; Dr. Jose E. Gonzalez	Monterrey	Nuevo LEON
Netherlands	NKI/AvL	Amsterdam
Netherlands	UMC St Radboud	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Romania	Amethyst Cluj; Medical Oncology	Cluj County
Romania	Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala	Cluj Napoca
Romania	Centrul de Oncologie Sfantul Nectarie	Craiova
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Emergency County Clinical Hospital Ploiesti; Medical oncology	Ploiesti
Romania	Centrul de Oncologie Oncohelp	Timisoara
Russian Federation	AV Medical Ltd.	Sait-Petersburg Sankt Petersburg	Sankt Petersburg
Slovakia	Univerzitna nemocnica Bratislava; Oddelenie Klinickej Onkologie, Klinika Pneumologie A Ftizeologie	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav	Kosice
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Sweden	Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01	Stockholm
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Gazi University Medical Faculty, Oncology Hospital	Ankara
Turkey	Liv Hospital Ankara; Medical Oncology	Ankara
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
Turkey	Ac?badem Maslak Hastanesi Büyükdere	Sar?yer/?stanbul

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Brazil,  China,  Croatia,  France,  Greece,  India,  Italy,  Jordan,  Lebanon,  Mexico,  Netherlands,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the scores of EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L)	To evaluate health status utility scores of participants to inform pharmacoeconomic modeling using the EuroQol 5-Dimension Questionnaire (5-level version; EQ-5D-5L) index-based and visual analog scale (VAS) scores	Up to 7 Years
Primary	Progression-free survival (PFS) in participants with central nervous system (CNS) metastases at baseline	PFS is defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause whichever occurs first determined by a blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).	Up to 7 years
Secondary	Progression-free survival in the Central Nervous System (CNS-PFS)	CNS-PFS is defined as the time from randomization to the first documented disease progression in the CNS or death from any cause, whichever occurs first, as determined by the BIRC using RECIST v1.1	Up to 7 Years
Secondary	Overall response rate (ORR)	ORR is defined as the percentage of participants who attain Complete Response (CR) or Partial Response (PR) as assessed by the BIRC and the investigator per RECIST v1.1	Up to 7 Years
Secondary	Duration of response (DOR)	DOR is defined as the time from when response (CR or PR) is first documented to disease progression or death, whichever occurs first, as assessed by the BIRC and the investigator per RECIST v1.1	Up to 7 Years
Secondary	Progression-free survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause, whichever occurs first, as determined by the BICR and investigator using RECIST v1.1	Up to 7 years
Secondary	Overall survival (OS)	OS is defined as the time from randomization to death from any cause	Up to 7 Years
Secondary	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)		Up to 7 Years
Secondary	Percentage of participants with impact on lung cancer-specific symptoms assessed by the EORTC QLQ-LC13		Up to 7 Years
Secondary	Objective response rate in the CNS-ORR in participants with CNS metastases at baseline	CNS-ORR is defined as the percentage of participants who attain CR or PR for lesions in the CNS, as determined by the BIRC per RECIST v1.1	Up to 7 Years
Secondary	Duration of response in the CNS (CNS-DOR) in participants with CNS metastases at baseline	CNS-DOR is defined as the time from when a CNS response (CR or PR) is first documented to disease progression in the CNS, as determined by the BIRC per RECIST v1.1	Up to 7 Years
Secondary	Percentage of participants with Adverse Events and Serious Adverse Events and Adverse Events leading to dose modifications/interruptions, study drug withdrawal or death	Assessed by the investigator according to the NCI CTCAE v5.0	Up to 7 Years