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

Study Purpose

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 Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04603807
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hoffmann-La Roche
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Clinical Trials
Principal Investigator Affiliation	Hoffmann-La Roche
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Brazil, China, Croatia, France, Germany, Greece, India, Italy, Jordan, Lebanon, Mexico, Netherlands, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand, Turkey
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Carcinoma, Non-Small-Cell Lung

Arms & Interventions

Arms

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.

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.

Interventions

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.

Drug: - Crizotinib

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Hospital Sao Rafael - HSR, Salvador, Bahia, Brazil

Status

Recruiting

Address

Hospital Sao Rafael - HSR

Salvador, Bahia, 41253-190

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