Tomotherapy 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 tomotherapy 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 tomotherapy 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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Tomotherapy 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: tomotherapy


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: experimental arm<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. Intervention：tomotherapy | Radiation: tomotherapy<br>* Tomotherapy: 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; 3. multiple lesions with large lesion: whole brain radiation (WBRT) with 40Gy/2Gy/20f and concurrent boost of 60Gy/3Gy/20f of the lesions. TMZ is used if necessary: concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/ m2*5d, q28d, up to 6cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Using RTOG9508 criteria, Tumor control is defined as CR+PR+SD | 2-3 months after radiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | up to 3 years | 
| progress free survival rate |  | up to 1 year | 
| local control rate |  | up to 1 year | 
| intracranial progress free survival rate |  | up to 1 year | 
| adverse event |  | from the day of radiation, up to 6 months | 
| cause of death |  | 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, tomotherapy