A Clinical Trial on Whole-brain Radiotherapy With Temozolomide Concurrent Chemotherapy or Avoidance of Hippocampus for Patients of Brain Metastases

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects on neurocognitive function of whole-brain radiotherapy (WBRT) with/without TMZ concurrent chemotherapy or avoidance of hippocampus for patients of brain metastases, as well as the feasibility and risk of avoidance of hippocampus during whole-brain radiotherapy.

Detailed Description
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This is a phase II randomized clinical trial. It is reported that avoidance of hippocampus during whole-brain radiotherapy (WBRT) had benefits in preservation of memory for patients, and the use of concurrent TMZ in radiotherapy for patients with brain metastases benefited for treating outcome. The purpose of this study is to evaluate the effects on neurocognitive function of whole-brain radiotherapy with/without TMZ concurrent chemotherapy or avoidance of hippocampus for patients of brain metastases, as well as the feasibility and risk of avoidance of hippocampus during whole-brain radiotherapy.

Official Title
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Effectiveness and Safety of Whole-brain Radiotherapy With/Without TMZ Concurrent Chemotherapy or Avoidance of Hippocampus for Patients of Brain Metastases: a Multi-institutional, Randomized Controlled Clinical Trial

Conditions
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Brain Metastasis, Radiation Therapy Complication

Intervention / Treatment
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* Drug: TMZ
* Radiation: WBRT with avoidance of hippocampus
* Radiation: WBRT without avoidance of hippocampus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary lesions diagnosed by pathology or cytology Brain metastases confirmed by brain MRI or CT(>3 brain metastases） Brain metastases beyond 5mm of hippocampus Male or female patients with age between 18 and 75 years old Karnofsky Performance Scores ≥ 60 Expected survival ≥ 6 months No previous brain surgery or brain radiotherapy Without dysfunction of heart, lung, liver, kidney and hematopoiesis The primary carcinoma is under control Exclusion Criteria: MMSE score <27 Dysfunction of heart, lung, liver, kidney or hematopoiesis Severe neurological, mental or endocrine diseases History of alcohol or drug abuse within 3 months Visual or hearing dysfunction, low education level, or other reasons leading to not capable of taking the MMSE test Currently under treatment may effect patients' neurocognitive functions Patients participated in clinical trials of other drugs within last 3 months Other unsuitable reason

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WBRT<br>Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy without avoidance of hippocampus applied. | Radiation: WBRT without avoidance of hippocampus<br>* Whole brain radiotherapy of 30Gy/10f by IMRT, with or without boost. The dose of hippocampus is not considered.<br>|
| Experimental: WBRT with avoidance of hippocampus<br>Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with avoidance of hippocampus applied. | Radiation: WBRT with avoidance of hippocampus<br>* Whole brain radiotherapy of 30Gy/10f by IMRT (Intensity Modulation Radiated Therapy), with or without boost. The maximum dose of hippocampus should be no more than 18Gy.<br>|
| Experimental: WBRT with TMZ<br>Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with concurrent TMZ chemotherapy applied. | Drug: TMZ<br>* TMZ 75mg/m2/d from the 1st day to the last day of radiotherapy<br>* Other names: temozolomide;Radiation: WBRT without avoidance of hippocampus<br>* Whole brain radiotherapy of 30Gy/10f by IMRT, with or without boost. The dose of hippocampus is not considered.<br>|
| Experimental: WBRT with avoidance of hippocampus and TMZ<br>Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with avoidance of hippocampus and concurrent TMZ chemotherapy applied. | Drug: TMZ<br>* TMZ 75mg/m2/d from the 1st day to the last day of radiotherapy<br>* Other names: temozolomide;Radiation: WBRT with avoidance of hippocampus<br>* Whole brain radiotherapy of 30Gy/10f by IMRT (Intensity Modulation Radiated Therapy), with or without boost. The maximum dose of hippocampus should be no more than 18Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of neurocognitive function between baseline and 4 months after radiotherapy | Neurocognitive function is evaluated by Minimum Mental State Examination (MMSE) | baseline; four months after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on response rate | Response is evaluated on basis of RECIST | baseline; One, two, four, six, and twelve months after radiotherapy | 
| The tolerance of radiotherapy with TMZ concurrent chemotherapy | Adverse effects are evaluated by CTCAE 4.0 criteria | baseline; once a week through during radiotherapy, up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain metastasis, whole-brain radiotherapy, TMZ, avoidance of hippocampus