Hypofractionated Radiotherapy With Concurrent Temozolomide for Large Brain Metastases: a Multi-center Randomized Phase III Trial
Overview
- Phase
- Phase 3
- Intervention
- Temozolomide
- Conditions
- Brain Metastases
- Sponsor
- Chinese Academy of Medical Sciences
- Enrollment
- 224
- Locations
- 1
- Primary Endpoint
- intracranial progression free survival (IPFS) rate
- Last Updated
- 6 years ago
Overview
Brief Summary
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
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.
Investigators
Jianping Xiao
Principal Investigator
Chinese Academy of Medical Sciences
Eligibility Criteria
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.
Arms & Interventions
CRT group
patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy plus concomitant Temozolomide.
Intervention: Temozolomide
CRT group
patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy plus concomitant Temozolomide.
Intervention: hypofractionated radiotherapy
RT group
patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy alone.
Intervention: hypofractionated radiotherapy
Outcomes
Primary Outcomes
intracranial progression free survival (IPFS) rate
Time Frame: up to 2 years
IPFS was defined as the interval from the beginning of radiation to any intracranial progression
Secondary Outcomes
- local control rate(up to 2 years)
- Brain metastasis-specific survival (BMSS) rate(up to 2 years)
- overall survival (OS) rate(up to 2 years)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and NRG/RTOG CNS toxicities criteria(acute toxicities: up to 3 months after RT; Late toxicities: up to 2 years after RT)