Non-small cell lung cancer with ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene rearrangements MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Entrectinib
Product Code: RO7102122 - F04/F06/F10/F14/F24
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ENTRECTINIB
Current Sponsor code: RO7102122
Concentration unit: mg milli
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Age = 18 years •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. Patients who received brain irradiation must have completed whole brain radiotherapy at least 14 days prior and/or stereotactic radiosurgery at least 7 days prior to the start of entrectinib treatment •Measurable systemic disease according to RECIST v1.1 •Patients with measurable and non-measurable CNS lesions per RECIST v1.1, including leptomeningeal carcinomatosis, are eligible, provided that the patient is neurologically stable for at least 1 week prior to the first dose of study treatment. Note: Previously irradiated CNS lesions cannot be selected as target (measurable) lesions •Life expectancy of at least 12 weeks •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 •Adequate hematologic, renal, liver function •Recovery from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment •Ability to comply with the study protocol, in the investigator’s judgment •Ability to swallow entrectinib and crizotinib intact without chewing, crushing, or opening the capsules •For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for up to 5 weeks after the final dose of entrectinib or for at least 90 days after the final dose of crizotinib •For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 176 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: •Current participation in another therapeutic clinical trial •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 QT interval •History of additional risk factors for torsades de pointes •Grade =2 peripheral sensory neuropathy •Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis •Previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC) •Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy •Active GI disease or other malabsorption syndrome that would reasonably impact drug absorption •History of prior therapy-induced pneumonitis •Any condition (in the past 3 months) that would interfere with the determination of safety or efficacy of study treatments •Known active infections that would interfere with the assessment of safety or efficacy of study treatments (bacterial, fungal or viral), with the exceptions of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections •History of hypersensitivity to any of the additives in the entrectinib and/or crizotinib drug formulations •Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of entrectinib or crizotinib •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 or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study •Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of entrectinib compared with crizotinib in patients who have ROS1 rearrangement-positive NSCLC with CNS metastases at baseline;Secondary Objective: •To evaluate the efficacy of entrectinib compared with crizotinib in patients who have ROS1 rearrangement-positive NSCLC in the whole study population (ITT) •To evaluate the efficacy of entrectinib compared with crizotinib in patients who have ROS1 rearrangement-positive NSCLC with CNS metastases at baseline •To evaluate the safety of entrectinib compared with crizotinib in patients who have ROS1 rearrangement-positive NSCLC •To evaluate health status utility scores of patients treated with entrectinib to inform pharmacoeconomic modeling using the EuroQol 5-Dimension Questionnaire (5-level version; EQ-5D-5L) index-based and visual analog scale (VAS) scores;Primary end point(s): 1.Progression-free survival (PFS) in patients with CNS metastases at baseline, 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 a blinded independent review committee (BIRC) using RECIST v1.1;Timepoint(s) of evaluation of this end point: 1.Up to 7 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Progression-free survival in the CNS (CNS-PFS), 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 2.Overall response rate (ORR), defined as the percentage of patients who attain CR or PR, as assessed by the BIRC and the investigator per RECIST v1.1 3.Duration of response (DOR), 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 4.Progression-free survival (PFS), 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 5.Overall survival (OS), defined as the time from randomization to death from any cause 6.Impact on functioning, including health-related quality of life, using the Global Health Status/Quality of Life (GHS/QoL), the Physical Functioning (PF) and Role Function (RF) scores, as assessed by the EORTC QLQ-C30 and analyzed as a time to first and confirmed clinically meaningful deterioration 7.Impact on lung cancer-specific symptoms, as assessed by the EORTC QLQ-LC13 8.Objective response rate in the CNS (CNS-ORR), defined as the percentage of patients who attain CR or PR for lesions in the CNS, as determined by the BICR per RECIST v1.1 9.Duration of response in the CNS (CNS-DOR), 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 BICR per RECIST v1.1 10.Incidence, type, timing, relatedness and severity of adverse events, including serious adverse events and adverse events leading to dose modifications/interruptions, study drug withdrawal or death, as assessed by the investigator according to the National Cancer Institute | — |
Countries
Brazil, China, Colombia, Croatia, France, Germany, Greece, Guatemala, India, Italy, Jordan, Lebanon, Mexico, Netherlands, Romania, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Turkey
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed