HFSRT With Concurrent TMZ for Large BMs

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

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.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy; Brain Metastases; Radiotherapy
• Intervention / Treatment: Drug: Temozolomide; Radiation: hypofractionated radiotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 224
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Chinese Academy of Medical Sciences
      • Contact: Jianping Xiao, Dr; Phone Number: 86-13811026919; Email: jpxiao8@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Jianping Xiao, Dr, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Anticipated): December 3, 2022
• Study Completion (Anticipated): December 3, 2022

Study Registration Dates

• First Submitted: December 9, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: LBM-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No