HFSRT With Concurrent TMZ for Large BMs

Study Overview
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Brief Summary
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A multi-center randomized phase III trial was conducted to investigate the feasibility and safety of adding temozolomide to hypofractionated stereotactic radiotherapy for large brain metastases.

Detailed Description
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A previous single arm phase II trial and propensity- matched study of our institution have shown that HFSRT combined with concurrent TMZ was safe and efficient for patients with BMs of ≥ 6cc in volume. The 1-year local control, intracranial progression free survival, progression free survival and overall survival rates were better than HFSRT alone group. Thus, the investigator conducted this randomized phase III trial to broad the sample size and verify our previous results. To finish the study in time, the investigator designed a multi-center trial.

Official Title
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Hypofractionated Radiotherapy With Concurrent Temozolomide for Large Brain Metastases: a Multi-center Randomized Phase III Trial

Conditions
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Brain Metastases, Chemotherapy, Radiotherapy

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: hypofractionated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologic or cytological diagnosis of primary tumor and conformed brain metastases by enhanced MRI or CT; the number of BMs ≤ 3 the tumor volume ≥6cc, or maximum diameter of BMs≥ 3cm; Karnofsky performance score (KPS)≥60, or KPS≥40 but simply caused by BMs; Age: 18-75 years old; Adequate function of major organs, and blood test reached the following level: WBC≥4.0x109/L, NEU≥1.5x109/L Hemoglobin≥110 g/L, Platelets≥100 x109/L; Liver function test results<1.5 times the institutional upper limit of normal (ULN); BUN and Cr: within the normal range. Exclusion Criteria: patient with other clinically significant diseases (e.g. myocardial infarction within the past 6 months, severe arrhythmia); unable or unwilling to comply with the study protocol; patient whose survival expectancy was less than 3 months; the large BM locates in brainstem; patient who anticipated in other clinical trials of brain metastases; the large lesions have been treated with SRT in other hospitals; pregnant patients or female patients whose HCG is positive.

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
Interventional Model Description: patients were randomized to 2 parallel groups, namely the concurrent chemoradiotherapy group and radiotherapy alone group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRT group<br>patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy plus concomitant Temozolomide. | Drug: Temozolomide<br>* 75mg/m2/d concurrent with radiotherapy, taken for at least 20 days.<br>Radiation: hypofractionated radiotherapy<br>* the regular radiation dose prescription is 52 Gy in 13 fractions or 52.5 Gy in 15 fractions.<br>|
| Active Comparator: RT group<br>patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy alone. | Radiation: hypofractionated radiotherapy<br>* the regular radiation dose prescription is 52 Gy in 13 fractions or 52.5 Gy in 15 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial progression free survival (IPFS) rate | IPFS was defined as the interval from the beginning of radiation to any intracranial progression | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local control rate | the control rate of treated lesions | up to 2 years | 
| Brain metastasis-specific survival (BMSS) rate | BMSS was defined as the internal from the beginning of RT to death caused by BM | up to 2 years | 
| overall survival (OS) rate | OS was defined as the internal from the beginning of RT to death caused by any reason | up to 2 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and NRG/RTOG CNS toxicities criteria | the toxicities caused by RT and (or) Chemotherapy | acute toxicities: up to 3 months after RT; Late toxicities: up to 2 years after RT |