- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03529084
Phase III Study of Nazartinib (EGF816) Versus Erlotinib/Gefitinib in First-line Locally Advanced / Metastatic NSCLC With EGFR Activating Mutations
A Randomized, Open-label, Phase III Study of Single Agent Nazartinib Versus Investigator's Choice (Erlotinib or Gefitinib) as First-Line Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent obtained prior to any screening procedures.
- Histologically documented locally advanced or metastatic, stage IIIB/ IIIC or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del)
- Provision of a tumor tissue sample to allow for retrospective analysis of EGFR mutation status
- No prior treatment with any systemic antineoplastic therapy in the advanced setting
- Recovered from all toxicities related to prior treatment
- Presence of at least one measurable lesion according to RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance ≤1
Meet the following laboratory values at the screening visit:
- Absolute Neutrophil Count ≥1.5 x 109/L
- Platelets ≥75 x 109/L
- Hemoglobin (Hgb) ≥9 g/dL
- Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula
- Total bilirubin ≤1.5 x ULN
- Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN
- Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤5.0 x ULN
Exclusion Criteria:
- Prior treatment with EGFR-TKI.
- Known T790M positive mutation. Any other known EGFR activating mutations other than L858R or ex19del. Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible.
- Symptomatic brain metastases
- History of interstitial lung disease or interstitial pneumonitis
- Any medical condition that would, in the investigator's judgment, the patient's in the study due to safety concerns, compliance with clinical study procedures or interpretation of study results
- Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years..
- Presence of clinically significant ophthalmologic abnormalities
- Bullous and exfoliative skin disorders of any grade
- Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
- Known history of testing positive for human immunodeficiency virus (HIV) infection
- Cardiac or cardiac repolarization abnormality
- Major surgery: ≤4 weeks to starting study treatment or who have not recovered from side effects of such procedure.
- Unable or unwilling to swallow tablets or capsules
- Female patients who are either pregnant or nursing
- Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.
- Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment.
Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: EGF816
Investigational treatment arm of EGF816 (nazartinib).
|
It will be administered orally daily.
Other Names:
|
Active Comparator: Investigator's Choice
Investigator's Choice (erlotinib or gefitinib).
|
Investigator's choice between erlotinib or gefitinib. These will be locally sourced. Erlotinib will be administered orally daily. Gefitinib will be administered orally daily. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS) by Blinded independent review committee (BIRC)
Time Frame: Approximately 3 years
|
PFS using central BIRC assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by BIRC per RECIST 1.1) or death due to any cause, whichever occurs first.
|
Approximately 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Approximately 6 years
|
Overall survival is defined as the time from date of randomization to date of death due to any cause.
|
Approximately 6 years
|
PFS by investigator
Time Frame: Approximately 3 years
|
PFS by Investigator assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by Investigator per RECIST 1.1) or death due to any cause, whichever occurs first.
|
Approximately 3 years
|
PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1
Time Frame: Approximately 4 years
|
PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1 is defined as time from date of randomization to the first documented disease progression (clinical or radiologic) as per investigator assessment on next-line therapy or death from any cause, whichever occurs first.
|
Approximately 4 years
|
Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC
Time Frame: Approximately 3 years
|
Time to progression in CNS, defined as time from date of randomization to the date of first documented progression of brain metastases as assessed by central neuro-radiologist BIRC per modified RECIST 1.1 for patients with at least one non-measurable and/or measurable lesion in the brain at baseline.
|
Approximately 3 years
|
Overall response rate (ORR) by central BIRC
Time Frame: Approximately 3 years
|
ORR in accordance with RECIST 1.1.
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)
|
Approximately 3 years
|
Duration of response (DOR) by central BIRC
Time Frame: Approximately 3 years
|
DOR is defined as the time from date of first documented response (CR and PR) to the date of the first documented progression or death due to underlying cancer, whichever occurs first.
|
Approximately 3 years
|
Disease control rate (DCR) by central BIRC
Time Frame: Approximately 3 years
|
DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD).
|
Approximately 3 years
|
Time to response (TTR) by central BIRC
Time Frame: Approximately 3 years
|
TTR is defined as the time from the date of randomization to the first documented response CR or PR.
|
Approximately 3 years
|
CNS ORR per central neuro-radiologist BIRC
Time Frame: Approximately 3 years
|
CNS ORR in patients with brain metastases who have measurable disease in the brain at baseline review per modified RECIST 1.1
|
Approximately 3 years
|
CNS DoR per central neuro-radiologist BIRC
Time Frame: Approximately 3 years
|
CNS DoR in patients with brain metastases who have measurable disease in the brain at baseline per modified RECIST 1.1
|
Approximately 3 years
|
Charactise Plasma PK (Cmax) of EGF816
Time Frame: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Peak plasma concentration (Cmax) of EGF816 and its metabolite (LMI258)
|
Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Charactise Plasma PK (AUC) of EGF816
Time Frame: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Area under the plasma concentration versus time curve (AUC) of EGF816 and its metabolite (LMI258)
|
Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Charactise Plasma PK (t1/2) of EGF816
Time Frame: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Elimination half life (t1/2) of EGF816 and its metabolite (LMI258)
|
Day 1 of Cycles 1 to 6 inclusive (21 day cycle)
|
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-C30 Questionnaire
Time Frame: Approximately 4 years
|
HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life score
|
Approximately 4 years
|
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-LC13 Questionnaire
Time Frame: Approximately 4 years
|
HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 quality of life score
|
Approximately 4 years
|
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by EuroQoL-5 Dimension-5 (EQ-5D-5L) Questionnaire
Time Frame: Approximately 4 years
|
Global health status/quality of life score of the EQ-5D-5L
|
Approximately 4 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
- Gefitinib
- Nazartinib
Other Study ID Numbers
- CEGF816A2302
- 2017-003998-34 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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