Stereotactic Radiotherapy Plus Temozolomide for Refractory Brain Metastases

Study Overview
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Brief Summary
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This clinical trial was designed to investigate the efficiency and toxicity of fractionated stereotactic radiotherapy(FSRT) combined with Temozolomide(TMZ) for refractory brain metastases.

Detailed Description
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This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of FSRT plus TMZ for refractory brain metastases, which are defined as A: multiple brain metastases(≥3 lesions); B: large brain metastases(with one lesion's volume is no smaller than 6cc or the longest diameter is no shorter than 3cm); C: meningeal metastases.

Official Title
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Fractionated Stereotactic Radiotherapy Combined With Temozolomide for Refractory Brain Metastases: A Single-arm, Single-center Phase II Trial

Conditions
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Brain Metastases

Intervention / Treatment
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* Radiation: Fractionated Stereotactic Radiotherapy
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of primary tumor and conformed brain metastases by enhanced MRI or CT the lesion number is no less than 3; or the tumor volume is no smaller than 6cc; or tumor diameter is no shorter than 3cm; or uncontrolled brain tumor after whole brain radiotherapy(WBRT); or the tumor is adjacent to essential structures of the brain, such as brain stem, optic chiasma, optic tract, etc. KPS ≥60，or KPS ≥40 and the limitation of motion is simply caused by brain tumor that is adjacent to the motor function areas. Age: 18-75 years old. Adequate end-organ function: WBC≥4.0x109/L Neu ≥ 1.5x109/L Hemoglobin ≥ 110 g/L Platelets ≥100 x109/L Total bilirubin ≤ 1.5x ULN AST and ALT ≤ 1.5x ULN BUN and Cr: within the normal range Exclusion Criteria: Other clinically significant diseases (e.g.myocardial infarction within the past 6 months, severe arrhythmia). Unable or unwilling to comply with the study protocol. The expected survival time is less than 3 months. Patients who are anticipated in other clinical trials of brain metastases. Patients who has been treated with SRT in other hospitals Pregnant patients or female patients whose HCG is positive Unsuitable to participate in study, that in the opinion of the treating physician.

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: Refractory Brain Metastases<br>Group A: multiple brain metastases: no less than 3 lesions in the brain Group B: Large Brain Metastases: the volume of lesion is no smaller than 6cc or the maximum diameter of the lesion is no shorter than 3cm Group C:Meningeal Metastases | Radiation: Fractionated Stereotactic Radiotherapy<br>* The regular fraction modes were as follows: a. lesions≥3 cm：52Gy/4Gy/13f or 52.5Gy/3.5Gy/15f; b. lesions<2cm：36Gy/12Gy/3f or 24Gy/24Gy/1f; for lesions located in function areas, it would be adjusted to 40Gy/8Gy/5f; c. lesions 2-3cm：40-48Gy/8-10Gy/6-4f; d. lesions located in brainstem：50-60Gy/2.5-3Gy/20f.<br>* Other names: FSRT;Drug: Temozolomide<br>* concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/m2*5d, q28d, 6cycles<br>* Other names: TMZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial progress free survival rate | defined as no progress of the treated lesions and no distant progress in the brain | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | up to 3 year | 
| progress free survival rate |  | up to 1 year | 
| local control rate |  | up to 1 year | 
| disease control rate (DCR) | Using RTOG9508 criteria, Tumor control is defined as CR+PR+SD | 2-3 months after radiation | 
| adverse event | assessed by CTCAE criteria, v4.0 and RTOG criteria of the central nervous system | from the day of radiation to the end of adjuvant TMZ，up to 6 months | 
| causes of death | collect the data of causes of death and analyze | from the day of radiation to death date, up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple brain metastases, large brain metastases, meningeal metastases, fractionated stereotactic radiotherapy, temozolomide