- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05167851
The Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer
A Multicentre Two-arm, Phase II Trial Assessing the Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer
This is based on the observations that disease progression under EGFR(Epidermal Growth Factor Receptor) targeting TKI(Tyrosine Kinase Inhibitor) most frequently occurs at the original sites of metastatic disease and that the majority of patients shows disease progression in a limited number of metastatic lesions, a situation defined as oligoprogression.
All studies reported a significantly and clinically relevant improved OS(Overall Survival) or PFS(Period Free Survival) for adding locally ablative therapy to standard of care systemic therapy. However, these studies included only very few NSCLC(non small cell lunc cancer) patients with activating driver mutations and the benefit of adding upfront local radiotherapy might be smaller or larger in this NSCLC(non small cell lunc cancer) patient population with activating driver mutations and treatment with TKIs(Tyrosine Kinase Inhibitor) smaller because of the higher systemic efficacy of TKIs(Tyrosine Kinase Inhibitor) compared to chemotherapy or larger because the benefit of local treatment might become most obvious if potential microscopic disease is successfully controlled by TKI(Tyrosine Kinase Inhibitor)s .Consequently, there is a clinical need to evaluate locally ablative therapy in oligometastatic EGFR (Epidermal Growth Factor Receptor) -mutant NSCLC(non small cell lunc cancer) patients and simultaneously a strong rational that this population might benefit in particular from a combined modality treatment: the benefit of locally ablative therapy is expected to be largest in situations of effective systemic therapies to control locally untreated microscopic disease which is true for EGFR (Epidermal Growth Factor Receptor) targeting.
The investigator therefore propose a prospective two-arm phase II study, which aims to evaluate safety and efficacy of lazertinib combined with early locally ablative radiotherapy of all cancer sites in patients with synchronous oligometastatic (primary tumour and maximum 5 metastases) EGFR (Epidermal Growth Factor Receptor) -mutant (exon 19 deletion or exon 21 L858R) NSCLC. Eradication of all macroscopic cancer sites at the time of primary diagnosis by combined modality treatment is expected to decrease the risk of resistance development with only microscopic disease potentially remaining. This will result in an improvement of PFS(Period Free Survival) and OS(Overall Survival) without added high-grade toxicity.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sun min Lim
- Phone Number: +82-2227-8296
- Email: limlove2008@yuhs.ac
Study Locations
-
-
-
Seoul, Korea, Republic of
- Yonsei University Health system, Severance Hospital
-
Contact:
- Sun min Lim
- Phone Number: +82-2227-8296
- Email: limlove2008@yuhs.ac
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation.
- Presence of the sensitising EGFR-mutation (exon 19 deletion and/or L858R) detected by an accredited laboratory.
- Synchronous oligometastatic stage IV disease (max 5 lesions)
- Measurable disease as defined according to RECIST v1.1
- All lesions amenable for radical radiotherapy according to local judgment
- Age ≥18 years
- ECOG performance status 0-2
- Life expectancy ≥12 months
Adequate haematological function:
- Hemoglobin 90 g/L
- Absolute neutrophil count (ANC) 1.5× 109/L
- Platelet count 100× 109/L
Adequate renal function:
Serum creatinine 1.5x ULN or creatinine clearance ≥50 mL/min (calculated according to Cockcroft-Gault, see below). Confirmation of creating clearance is only required when serum creatinine is >1.5x ULN.
Adequate liver function:
- ALT and AST 2.5× ULN. If the patient has liver metastases, ALT and AST must be ≤5× ULN
- Total serum bilirubin 1.5× ULN. If the patient has documented Gilbert's syndrome (unconjugated hyperbilirubinaemia) 3× ULN.
- Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment.
- Written IC for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention.
Exclusion Criteria:
- Prior chemotherapy, immunotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection of CNS or adrenal metastases)
- More than 5 distant oligometastases (any second intra-thoracic lesion will count as a distant metastasis; regional nodal metastases will not count to the 5 oligometastases) and more than 2 intra-thoracic lesions.
- Brain metastases not amenable for radiosurgery or neurosurgery
- Presence of leptomeningeal metastases
- Symptomatic spinal cord compression
- Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques.
- Currently receiving (or unable to stop use prior to receiving the first dose of lazertinib treatment) medications or herbal supplements known to be potent CYP3A4 inducers that cannot be stopped before enrolment and for the duration of the trial.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol.
Patients with a resolved or chronic HBV infection are eligible if they are:
- Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG] or
- Positive for HBsAg, negative for HBeAg but for >6 months have had transaminases levels below ULN and HBV DNA levels below 2000 IU/mL (i.e., are in an inactive carrier state).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of lazertinib
Any of the following cardiac criteria:
QTcF >470 msec obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value (QTcF: corrected QT interval using Fredericia's formula).
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block or second degree heart block).
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP).
- Past medical history of ILD, drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- Idiopathic pulmonary fibrosis which is a contraindication to lung radiation.
- History of hypersensitivity to active or inactive excipients of lazertinib or drugs with a similar chemical structure or class to lazertinib.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements Women who are pregnant or in the period of lactation.
- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method (Please refer to 8.4 for highly effective contraceptive methods) during the trial and up to 6 weeks for women and up to 4 months for men, after discontinuing lazertinib treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lazertinib, a combination group of SBRT
|
* Lazertinib 240mg once a day(QD) oral(PO) -If there is no disease progression or unacceptable toxicity, treatment is performed at 1 cycle (28 days) interval . This is expected to be an average of one year. |
Active Comparator: Lazertinib single administration group
* Lazertinib 240mg once a day(QD) oral(PO) -If there is no disease progression or unacceptable toxicity, treatment is performed at 1 cycle (28 days) interval . This is expected to be an average of one year. |
* Lazertinib 240mg once a day(QD) oral(PO) -If there is no disease progression or unacceptable toxicity, treatment is performed at 1 cycle (28 days) interval . This is expected to be an average of one year. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival (PFS)
Time Frame: every 8 weeks after enrollment, an average of one year
|
The time to recurrence/progression/death and From start of Lazertinib to documented radiographic relapse/progression by RECIST 1.1 criteria
|
every 8 weeks after enrollment, an average of one year
|
Progression free survival (PFS)
Time Frame: disease progression, an average of one year
|
The time to recurrence/progression/death and From start of Lazertinib to documented radiographic relapse/progression by RECIST 1.1 criteria
|
disease progression, an average of one year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: Every 12 weeks after the end of the study , which will be conducted in about 3 years.
|
Overall survival (OS) is defined as the time from the date of enrolment until death from any cause.
Censoring will occur at the last follow-up date.
|
Every 12 weeks after the end of the study , which will be conducted in about 3 years.
|
Distant Progression free survival (Distant PFS)
Time Frame: At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Distant PFS is defined as the time from date of enrollment until development of new metastases, excluding oligometastases diagnosed at enrolment.
|
At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Objective response rate (ORR)
Time Frame: At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Objective response rate (ORR) is defined as the percentage of patients that achieve a best overall response [complete response (CR) or partial response (PR)] according to RECIST v1.1 from enrolment across all trial assessment time-points.
|
At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Duration of Response (DoR)
Time Frame: At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Duration of Response (DoR) is defined as the interval from the date of first documentation of objective response (CR or PR, according to RECIST v1.1) to the date of first documented progression, relapse or death.
|
At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Adverse event according to CTCAE(Common Terminology Criteria for Adverse Event) v5.0
Time Frame: Screening, every cycle visit and End of study, and evaluation up to 6 weeks after End of the study. This is is expected to be an average of one year.
|
AE captured by CYCAE 5.0 until after 30days of last administration.
|
Screening, every cycle visit and End of study, and evaluation up to 6 weeks after End of the study. This is is expected to be an average of one year.
|
Pattern of disease progression
Time Frame: At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
The pattern of disease progression is defined as the site of first progression: None, locoregional, distant (bone, brain, liver, etc) or both locoregional and distant, evaluated up to 18-months post enrollment.
|
At screening, every 8 weeks after enrollment, and when the disease progresses. This is expected to be an average of one year.
|
Exploratory analysis (Analysis of acquired resistance mechanism through cfDNA)
Time Frame: At Screening and disease progression. This is expected to be an average of one year.
|
• Analysis of acquired resistance mechanisms to lazertinib plus radiotherapy at the time of progression using tumor/liquid cfDNA biopsy
|
At Screening and disease progression. This is expected to be an average of one year.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sun Min Lim, Yonsei University Health system, Severance Hospital
Publications and helpful links
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
- Protein Kinase Inhibitors
- Lazertinib
Other Study ID Numbers
- 4-2021-1227
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
Clinical Trials on Non Small Cell Lung Cancer
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Stanford UniversityAstraZenecaRecruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Lung Cancer Stage IIUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
Clinical Trials on Lazertinib , a combination group of SBRT
-
Myung-Ju AhnRecruitingNSCLCKorea, Republic of
-
Bukwang PharmaceuticalActive, not recruitingParkinson Disease | DyskinesiasUnited States
-
University of ArizonaCompleted
-
Hospital Son EspasesLinde AGCompletedPulmonary Disease, Chronic ObstructiveSpain
-
Hospices Civils de LyonCompletedInfection, Bacterial | Infection ViralFrance
-
EMD SeronoTerminated
-
Stanford UniversityNot yet recruitingHeart FailureUnited States
-
Hospital Universitario San Juan de AlicanteCompleted
-
Shengjing HospitalJiangsu HengRui Medicine Co., Ltd.Active, not recruiting
-
Georgetown UniversityEnrolling by invitation