MR-Linac Guided Adaptive FSRT for Brain Metastases From Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This Phase II study is to determine the efficacy and safety of MR-Linac Guided Adaptive fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases in non-small cell lung cancer.

Detailed Description
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This Phase II study is to determine the efficacy and safety of MR-Linac Guided Adaptive fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases in non-small cell lung cancer. Patients will receive FSRT (30Gy in 5 fractions) on the MR-Linac treatment machine. The primary end point is 1-year intracranial progression-free survival. The secondary end points are objective response rate, 1-y PFS, 1-y OS, perilesional edema of brain metastases, quality of life, safety of treatment, dose coverage of targets and dose to normal organs.

Official Title
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A Prospective, Phase II Study of MR-Linac Guided Adaptive Fractionated Stereotactic Radiotherapy for Brain Metastases From Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Combination Product: Unity-based MR-Linac guided FSRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-75 years Histologically or cytologically confirmed non-small cell lung cancer 1-10 metastases on contrast-enhanced MRI Radiotherapy for extracranial lesions is permitted Tyrosine kinase inhibitors (TKI) are permitted in patients with progression of intracranial metastases during previous TKI therapy Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Normal function of organs and bone marrow within 14 days: Total bilirubin 1.5 times or less the upper limits of normal (ULN); AST and ALT 1.5 times or less the ULN; absolute neutrophil count≥ 500 cells/mm3; creatinine clearance rate(CCR) ≥45 mL/min; Platelet count≥50,000 cells/mm3; international normalized ratio(INR) ≤1.5#Prothrombin Time (PT)≤ 1.5 × ULN Informed-consent Exclusion Criteria: Small cell carcinoma of lung Intracranial metastases needed surgical decompression Patients with contraindications for MRI Previous radiotherapy or excision for intracranial metastases The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava) A cavity over 2cm in diameter of primary tumor or metastasis Bleeding tendency or coagulation disorder Hemoptysis (1/2 teaspoon blood/day) happened within 1 month The use of full-dose anticoagulation within the past 1 month Severe vascular disease occurred within 6 months Gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months Uncontrolled hypertension (systolic > 150mmHg and/or diastolic > 100mmHg) Major surgery within 28 days or minor surgery or needle biopsy within 48 hours Urine protein 3-4+, or 24h urine protein quantitative >1g Severe uncontrolled disease Uncontrollable seizure or psychotic patients without self-control ability Women in pregnancy, lactation period Other not suitable conditions determined by the investigators

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: MR-Linac Guided Adaptive FSRT<br>Patients will receive FSRT (30Gy in 5 fractions) on the MR-Linac treatment machine. | Combination Product: Unity-based MR-Linac guided FSRT<br>* The FSRT was delivered using the Unity-based MR-Linac treatment machine, with a total dose of 30Gy in 5 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year intracranial progression-free survival |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 2 months | 
| 1-year progression-free survival |  | 1 year | 
| 1-year overall survival |  | 1 year | 
| Rate of participants with perilesional edema of brain metastases evaluated byT2-weighted MRI |  | 1 year | 
| Quality of life evaluated by EORTC quality of life questionnaire |  | 1 year | 
| Rate of patients with treatment-related adverse events evaluated by CTCAE v4.0 |  | 1 year | 
| Dose coverage to targets |  | 2 months | 
| Dose to normal organs |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, MR-Linac, Fractionated stereotactic radiation therapy, Brain metastase