Stereotactic Radiotherapy Plus Temozolomide for Refractory Brain Metastases (SRTRBM)

Fractionated Stereotactic Radiotherapy Combined With Temozolomide for Refractory Brain Metastases: A Single-arm, Single-center Phase II Trial

This clinical trial was designed to investigate the efficiency and toxicity of fractionated stereotactic radiotherapy(FSRT) combined with Temozolomide(TMZ) for refractory brain metastases.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Fractionated Stereotactic Radiotherapy; Drug: Temozolomide

Detailed Description

This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of FSRT plus TMZ for refractory brain metastases, which are defined as A: multiple brain metastases(≥3 lesions); B: large brain metastases(with one lesion's volume is no smaller than 6cc or the longest diameter is no shorter than 3cm); C: meningeal metastases.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Chinese Academy of Medical Sciences

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 cytologic diagnosis of primary tumor and conformed brain metastases by enhanced MRI or CT
• the lesion number is no less than 3; or the tumor volume is no smaller than 6cc; or tumor diameter is no shorter than 3cm; or uncontrolled brain tumor after whole brain radiotherapy(WBRT); or the tumor is adjacent to essential structures of the brain, such as brain stem, optic chiasma, optic tract, etc.
• KPS ≥60，or KPS ≥40 and the limitation of motion is simply caused by brain tumor that is adjacent to the motor function areas.
• Age: 18-75 years old.
• Adequate end-organ function:

WBC≥4.0x109/L Neu ≥ 1.5x109/L Hemoglobin ≥ 110 g/L Platelets ≥100 x109/L Total bilirubin ≤ 1.5x ULN AST and ALT ≤ 1.5x ULN BUN and Cr: within the normal range

Exclusion Criteria:

• Other clinically significant diseases (e.g.myocardial infarction within the past 6 months, severe arrhythmia).
• Unable or unwilling to comply with the study protocol.
• The expected survival time is less than 3 months.
• Patients who are anticipated in other clinical trials of brain metastases.
• Patients who has been treated with SRT in other hospitals
• Pregnant patients or female patients whose HCG is positive
• Unsuitable to participate in study, that in the opinion of the treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Refractory Brain Metastases; Group A: multiple brain metastases: no less than 3 lesions in the brain Group B: Large Brain Metastases: the volume of lesion is no smaller than 6cc or the maximum diameter of the lesion is no shorter than 3cm Group C:Meningeal Metastases

Radiation: Fractionated Stereotactic Radiotherapy; The regular fraction modes were as follows: a. lesions≥3 cm：52Gy/4Gy/13f or 52.5Gy/3.5Gy/15f; b. lesions<2cm：36Gy/12Gy/3f or 24Gy/24Gy/1f; for lesions located in function areas, it would be adjusted to 40Gy/8Gy/5f; c. lesions 2-3cm：40-48Gy/8-10Gy/6-4f; d. lesions located in brainstem：50-60Gy/2.5-3Gy/20f.; Other Names: FSRT; Drug: Temozolomide; concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/m2*5d, q28d, 6cycles; Other Names: TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intracranial progress free survival rate	defined as no progress of the treated lesions and no distant progress in the brain	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate		up to 3 year
progress free survival rate		up to 1 year
local control rate		up to 1 year
disease control rate (DCR)	Using RTOG9508 criteria, Tumor control is defined as CR+PR+SD	2-3 months after radiation
adverse event	assessed by CTCAE criteria, v4.0 and RTOG criteria of the central nervous system	from the day of radiation to the end of adjuvant TMZ，up to 6 months
causes of death	collect the data of causes of death and analyze	from the day of radiation to death date, up to 5 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Bi N, Ma Y, Xiao J, Zhang H, Xu Y, Tian Y, Li J, Zhang Y, Liu Q, Wang K, Deng L, Wang W, Chen X, Liu F, Zhao R, Yang S, Huang X, Yi J, Hu C, Li Y. A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases. Oncologist. 2019 Sep;24(9):e914-e920. doi: 10.1634/theoncologist.2018-0702. Epub 2019 Apr 17.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 10, 2016
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 13, 2016

Study Record Updates

• Last Update Posted (Actual): June 6, 2017
• Last Update Submitted That Met QC Criteria: June 5, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: temozolomide; multiple brain metastases; large brain metastases; meningeal metastases; fractionated stereotactic radiotherapy
• 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; Neoplasms, Second Primary; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: CH-H&N-003