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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04603807

Collaborator

(none)

220

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Entrectinib Drug: Crizotinib	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 30, 2021

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
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.	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.
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.	Drug: Crizotinib Crizotinib will be self-administered orally at a dose of 250 mg twice daily with or without food.

Arm

Intervention/Treatment

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.

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.

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.

Drug: Crizotinib

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) in participants with central nervous system (CNS) metastases at baseline [Up to 7 years]
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).

Secondary Outcome Measures

Progression-free survival in the Central Nervous System (CNS-PFS) [Up to 7 Years]
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
Overall response rate (ORR) [Up to 7 Years]
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
Duration of response (DOR) [Up to 7 Years]
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
Progression-free survival (PFS) [Up to 7 years]
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
Overall survival (OS) [Up to 7 Years]
OS is defined as the time from randomization to death from any cause
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]
Percentage of participants with impact on lung cancer-specific symptoms assessed by the EORTC QLQ-LC13 [Up to 7 Years]
Objective response rate in the CNS-ORR in participants with CNS metastases at baseline [Up to 7 Years]
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
Duration of response in the CNS (CNS-DOR) in participants with CNS metastases at baseline [Up to 7 Years]
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
Percentage of participants with Adverse Events and Serious Adverse Events and Adverse Events leading to dose modifications/interruptions, study drug withdrawal or death [Up to 7 Years]
Assessed by the investigator according to the NCI CTCAE v5.0

Other Outcome Measures

Change in the scores of EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L) [Up to 7 Years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital de Cancer de Barretos	Barretos	SP	Brazil	14784-400
2	Beijing Union Hospital	Beijing		China	100730
3	Jilin Cancer Hospital	Changchun		China	132013
4	Hunan Cancer Hospital	Changsha City		China	410013
5	The Second Xiangya Hospital of Central South University	Changsha		China	410011
6	West China Hospital, Sichuan University	Chengdu		China	610041
7	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China	510120
8	Harbin Medical University Cancer Hospital	Harbin		China	150081
9	Affiliated Hospital of Jining Medical University	Jining		China	272029
10	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City		China	210008
11	Guangxi Cancer Hospital of Guangxi Medical University	Nanning		China	530021
12	Shanghai Pulmonary Hospital	Shanghai		China	200433
13	Taihe Hospital of Hubei University of Medicine	Shiyan		China	442000
14	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
15	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
16	CHRU Lille	Lille		France	59037
17	Centre Leon Berard	Lyon		France	69008
18	Hopital Nord AP-HM	Marseille		France	13015
19	Hopital Larrey; Pneumologie	Toulouse		France	31059
20	Hopital Robert Schuman; Pneumologie	Vantoux		France	57070
21	Uoa Sotiria Hospital; Oncology	Athens		Greece	115 27
22	University Hospital of Larissa;Department of Medical Oncology	Larissa		Greece	411 10
23	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki		Greece	546 45
24	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
25	IRCCS Istituto Regina Elena (IFO); Oncologia Medica B	Roma	Lazio	Italy	00144
26	Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio	Italy	00152
27	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria	Italy	16132
28	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia	Italy	20141
29	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia	Italy	20162
30	ASST DI MONZA; Oncologia Medica	Monza	Lombardia	Italy	20900
31	Azienda Sanitaria Ospedaliera S Luigi Gonzaga; SSD Oncologia Polomonare (II PAD. IV PIANO)	Orbassano	Piemonte	Italy	10043
32	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana	Italy	56124
33	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto	Italy	35128
34	King Hussein Cancer Center	Amman		Jordan	1269
35	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco	Mexico	44280
36	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)	Mexico	03100
37	Superare; Centro de Infusion	Ciudad de México	Mexico CITY (federal District)	Mexico	06760
38	Hospital Universitario; Dr. Jose E. Gonzalez	Monterrey	Nuevo LEON	Mexico	64460
39	NKI/AvL	Amsterdam		Netherlands	1066 CX
40	UMC St Radboud	Nijmegen		Netherlands	6525 GA
41	Erasmus MC	Rotterdam		Netherlands	3015 GD
42	Centrul de Oncologie Oncohelp	Timisoara		Romania	300239
43	AV Medical Ltd.	Sait-Petersburg Sankt Petersburg	Sankt Petersburg	Russian Federation	196006
44	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña	Spain	15006
45	Hospital del Mar; Servicio de Oncologia	Barcelona		Spain	08003
46	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona		Spain	08908
47	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
48	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga		Spain	29011
49	Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01	Stockholm		Sweden	171 76
50	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana		Turkey	01230
51	Gazi University Medical Faculty, Oncology Hospital	Ankara		Turkey	06500
52	Liv Hospital Ankara; Medical Oncology	Ankara		Turkey	06680
53	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir		Turkey	35100
54	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya		Turkey	44280
55	Acıbadem Maslak Hastanesi Büyükdere	Sarıyer/İstanbul		Turkey	34457

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04603807

Other Study ID Numbers:

MO41552
2019-003859-11

First Posted:

Oct 27, 2020

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hoffmann-La Roche

ROS1 Non-small-cell lung

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Crizotinib

Entrectinib

Study Results

No Results Posted as of Aug 25, 2022