A Study of Furmonertinib Combined With Radiotherapy for Non-small Cell Lung Cancer With Oligoprogression

Study Overview
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Brief Summary
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This Phase II randomized study is to explore the efficacy and safety of Furmonertinib combined with radiotherapy for non-small cell lung cancer with oligoprogression after first-line EGFR-TKI therapy.

Detailed Description
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This Phase II randomized study is to explore the efficacy and safety of Furmonertinib combined with radiotherapy for non-small cell lung cancer with oligoprogression after first-line EGFR-TKI therapy. The first group will enroll NSCLC patients with oligoprogression after using the first/second generation EGFR-TKI. The participants will receive Furmonertinib 80mg and local radiotherapy as the following therapy. The other group will enroll NSCLC patients with oligoprogression after using the third generation EGFR-TKI. The participants will receive Furmonertinib 160mg and local radiotherapy as the following therapy.

Official Title
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A Phase II Single-arm Study of Furmonertinib Combined With Radiotherapy for Non-small Cell Lung Cancer With Oligoprogression After First-line EGFR-TKI Therapy

Conditions
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Non-small Cell Lung Cancer, Oligoprogressive

Intervention / Treatment
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* Drug: Furmonertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced or metastatic NSCLC who are diagnosed by histology or cytology and are not suitable for surgery or radiotherapy; After receiving the first or second generation of EGFR-TKI treatment, the disease is oligoprogressive with 3-5 lesions (with imaging evidence), and the mutation is T790M+ (histological or hematological specimens, ARMS detection method); After receiving osimertinib treatment in the past, the disease is oligoprogressive with 3-5 lesions (with imaging evidence), and the patient refused chemotherapy; 18-80 years old; ECOG PS 0-2 scores; Organ and bone marrow functions were generally normal within 30 days before enrollment, including:AST, ALT ≤ 2.5 × ULN or ≤ 5 × ULN (with liver metastasis); total bilirubin ≤ 1.5 × ULN; neutrophils absolute value ≥ 1500 cells/mm3; Creatinine clearance ≥45 mL/min; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥90g/L. The baseline has measurable lesions defined by the RECIST 1.1 standard, and the progressive lesions should be treated with local radiotherapy; the definition of the lesion number includes: When there are lesions on both adrenal glands, it is considered to be 2 metastases; Two consecutive vertebral lesions and a paravertebral lesion within 6 cm can be considered as one metastasis, and the non-contiguous vertebral lesions should be counted separately; The adjacent lesions in the liver, lung, and mediastinum can be considered as a metastasis if one isocenter can be used for irradiation; Intracranial lesions are counted as 1 metastasis. The patient signed an informed consent form. Exclusion Criteria: Severe or uncontrolled hypertension, diabetes, coronary artery stenosis, aortic dissection, aneurysm or acute bleeding disease; Any situation that increases the risk of QTc prolongation or arrhythmia; Left ventricular ejection fraction <50%; History of interstitial lung disease; FEV1%<30% or DLCO%<40%; Insertion of EGFR exon 20; The researcher believes that the patient is inappropriate to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furmonertinib 80mg combined with radiotherapy<br>This group will enroll NSCLC patients who are oligoprogressive after first/second generation EGFR-TKI therapy. These patients will receive furmonertinib 80mg combined with radiotherapy as following therapy. | Drug: Furmonertinib<br>* The different dose of furmonertinib will be given according to the generation of EGFR-TKI used as the first-line therapy. The doses and target volume of radiotherapy will be decided according to the oligoprogressive sites.<br>* Other names: Radiotherapy;|
| Experimental: Furmonertinib 160mg combined with radiotherapy<br>This group will enroll NSCLC patients who are oligoprogressive after third generation EGFR-TKI therapy. These patients will receive furmonertinib 160mg combined with radiotherapy as following therapy. | Drug: Furmonertinib<br>* The different dose of furmonertinib will be given according to the generation of EGFR-TKI used as the first-line therapy. The doses and target volume of radiotherapy will be decided according to the oligoprogressive sites.<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | From the first day of treatment to the day of progression or the day of death. | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | It was calculated from the first day of treatment to the day of death. | 2-year | 
| Failure pattern | Disease progression such as local recurrence or distant metastasis. | 2-year | 
| Safety evaluation | Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on. | 2 year after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, oligoprogressive, Furmonertinib combined with radiotherapy