Dose-painting Radiation for LA-NSCLC

Study Overview
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Brief Summary
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The study evaluated the effectiveness, safety and immune effects of dose-painting radiation in patients with locally advanced non-small cell lung cancer.

Detailed Description
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The study evaluated the effectiveness, safety and immune effects of dose-painting radiation in patients with locally advanced non-small cell lung cancer. The primary endpoint is PFS. Secondary points contains ORR, OS, HRQoL, and safety.

Official Title
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A Prospective Study on the Efficacy, Safety and Immune Effects of Dose-painting Radiation for Locally Advanced Non-small Cell Lung Cancer(LA-NSCLC)

Conditions
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Non-small Cell Lung Cancer Stage III, Non-small Cell Lung Cancer Stage II

Intervention / Treatment
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* Radiation: Dose-Painting Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or the legal representative of the patient can sign a written informed consent, and can understand and agree to follow the research requirements; The age at the time of signing the informed consent form is between 18 and 75 years old; It is diagnosed as non-small cell lung cancer by histology, and is suitable for radical radiotherapy: Stage II-Ⅲ (AJCC 8th edition [Rice et al., 2017]) inoperable NSCLC patients (not medically suitable for surgery or refuse surgical intervention); Measurable lesions that meet the definition of RECISTv1.1; ECOG physical status ≤ 2; Survival expectancy ≥ 3 months; Hemoglobin ≥100g/L, WBC≥4×109/L, platelet ≥100×109/L (or follow the standards of each center); Liver function: ALT, AST<1.5 times the upper limit of normal (ULN), total bilirubin<1.5×ULN; Renal function: serum creatinine <1.5×ULN; Pulmonary function: FEV1>50%, the percentage of DLCO (lung diffusion function) measured value and predicted value>80% mild to moderate lung function impairment. The patient has good compliance with the treatment and follow-up. Exclusion Criteria: There is evidence of distant metastasis (M1, AJCC 8th edition [Rice et al., 2017]); There is pleural effusion, pericardial effusion or ascites that is not clinically controlled and requires repeated drainage or medical intervention (within 2 weeks before randomization); Intolerance or resistance to the chemotherapy, targeted, and immunotherapy specified in the experimental protocol; Have received radiotherapy and surgical treatment; There were other active malignant tumors ≤ 2 years before enrollment, except for the specific cancers under study in this study and locally recurring cancers that have been cured (eg, resected basal cell or squamous cell skin cancer, superficial Bladder cancer, carcinoma in situ of the cervix or breast); A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including pulmonary fibrosis, acute lung diseases, etc.; Has suffered from other malignant tumors; Subjects who have received other drug trials within the past month; Pregnant or lactating women and women who refuse contraception during the treatment observation period; People with a history of severe allergies or idiosyncratic physique; Those with a history of severe lung or heart disease; Refusal or inability to sign the informed consent to participate in the trial; Drug or alcohol addicts; Personality or mental illness, lack of capacity for civil conduct or limited capacity for civil conduct.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Assigned Interventions<br>Radiation therapy: Dose-painting radiation Systemic treatment: Choose a systemic treatment plan according to the patient's genetic testing status (1) Chemotherapy Squamous cell carcinoma: Paclitaxel 135mg/m2 D1 + Cisplatin 25mg/m2 D1-3, every 21 days, a total of 2-4 cycles. Non-squamous cell carcinoma (adenocarcinoma, large cell carcinoma): Pemetrexed 500mg/m2 d1 + Cisplatin 75 mg/m2 d1-3, a total of 2-4 cycles. (2) Targeted therapy: According to the patient's genetic testing status, molecular targeted therapy such as EGFR-TKI and ALK inhibitors can be selected; (3) Immunotherapy: According to the patient's genetic testing status, immunotherapy such as PD1/PD-L1 inhibitors can be selected; | Radiation: Dose-Painting Radiation<br>* Radiation therapy: Delineation of target area: The primary tumor is delineated into different target areas according to the anatomical position of the tumor, including the central area tumor GTV-Tcentral and GTV-Tperipheral. Exposure dose: 1) GTV-Tcentral: 2.0～2.5Gy/f, bid, 10-13d, physical dose 40-65Gy 2) GTV-Tperipheral: 3.0～4.0Gy/f, bid, 10-13d, physical dose 60-104Gy 3) GTV-N (mediastinal lymph node): 2.0Gy/f, bid, 10-13d, physical dose 40-52Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FPS | progression-free survival (PFS) refers to the time from enrollment to the first recording of disease progression as determined by RECISTv1.1, or to death due to any cause (whichever occurs first). PFS will be analyzed in the ITT analysis set. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate, according to RECISTv1.1, the proportion of patients with CR or PR was determined. If the patient has not undergone a post-baseline assessment, it is considered unremission | up to 3 years | 
| OS | OS(Overall survival) refers to the time from enrollment to the first recorded death due to any cause (whichever occurs first). | up to 3 years | 
| HRQoL | HRQoL uses EORTCQLQ-C30 to assess the overall health of patients. The post-baseline score of the treatment group was studied, and the score changes from the baseline were summarized descriptively. | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, dose-painting radiation, non-small cell lung cancer