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
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT04603807
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Entrectinib 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. Crizotinib 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Overall survival (OS) Up to 7 Years OS is defined as the time from randomization to death from any cause
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
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
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
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 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
Percentage of participants with impact on lung cancer-specific symptoms assessed by the EORTC QLQ-LC13 Up to 7 Years
Trial Locations
- Locations (91)
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Oncocentro Serviços Médicos e Hospitalares Ltda
🇧🇷Fortaleza, Ceará, Brazil
Hospitais Integrados da Gavea S/A
🇧🇷Brasilia, Distrito Federal, Brazil
Oncocentro Belo Horizonte
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
🇧🇷Florianopolis, Santa Catarina, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Oncoclinicas Rio de Janeiro S.A.
🇧🇷Rio de Janeiro, Brazil
Beijing Union Hospital
🇨🇳Beijing, China
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