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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02832635

Collaborator

Fifth Affiliated Hospital, Sun Yat-Sen University (Other)

256

Enrollment

Locations

Arms

Duration (Months)

25.6

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastasis Radiation Therapy Complication	Drug: TMZ Radiation: WBRT with avoidance of hippocampus Radiation: WBRT without avoidance of hippocampus	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

256 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WBRT Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy without avoidance of hippocampus applied.	Radiation: WBRT without avoidance of hippocampus Whole brain radiotherapy of 30Gy/10f by IMRT, with or without boost. The dose of hippocampus is not considered.
Experimental: WBRT with avoidance of hippocampus Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with avoidance of hippocampus applied.	Radiation: WBRT with avoidance of hippocampus 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.
Experimental: WBRT with TMZ Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with concurrent TMZ chemotherapy applied.	Drug: TMZ TMZ 75mg/m2/d from the 1st day to the last day of radiotherapy Other Names: temozolomide Radiation: WBRT without avoidance of hippocampus Whole brain radiotherapy of 30Gy/10f by IMRT, with or without boost. The dose of hippocampus is not considered.
Experimental: WBRT with avoidance of hippocampus and TMZ Patients with brain metastases (>3 lesions) ; Whole-brain radiotherapy with avoidance of hippocampus and concurrent TMZ chemotherapy applied.	Drug: TMZ TMZ 75mg/m2/d from the 1st day to the last day of radiotherapy Other Names: temozolomide Radiation: WBRT with avoidance of hippocampus 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.

Outcome Measures

Primary Outcome Measures

Change of neurocognitive function between baseline and 4 months after radiotherapy [baseline; four months after radiotherapy]
Neurocognitive function is evaluated by Minimum Mental State Examination (MMSE)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Radiation Oncology, Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510000
2	Guangdong Three Nine Brain Hospital	Guangzhou	Guangdong	China	510000
3	Guangzhou First People's Hospital	Guangzhou	Guangdong	China	510000
4	Guangzhou People's Liberation Army Hospital 421	Guangzhou	Guangdong	China	510000
5	Panyu Central Hospital	Guangzhou	Guangdong	China	510000
6	The First Affiliated Hospital, Jinan University	Guangzhou	Guangdong	China	510000
7	The Affiliated Cancer Hospital Of Guangzhou Medical Collage	Guangzhou	Guangdong	China	510095
8	Guangdong Provincial Hospital Of Chinese Medicine	Guangzhou	Guangdong	China	510120
9	The First Affiliated Hospital Of Guangzhou Medical Collage	Guangzhou	Guangdong	China	510120
10	The Fifth Affiliated Hospital, Sun Yat-Sen University	Zhuhai	Guangdong	China	519000