The Role of Brain Radiotherapy in Patients With Asymptomatic Brain Metastasis in the Era of Targeted Therapy for NSCLC (BRATR)

December 9, 2019 updated by: Second Affiliated Hospital of Nanchang University

A Randomized Phase II Trial of Brain Radiotherapy Combined With Targeted Therapy in Patients With Asymptomatic NSCLC Brain Metastasis With Gene Sensitive Mutation

Brain metastasis is the most common neurological complication in tumor patients, and lung cancer is the most common tumor with brain metastasis. The prognosis of patients with non-small cell lung cancer with brain metastasis is poor. If not treated, the median survival time was about 1 month, the median survival time for steroid therapy was about 2 to 3 months, and the median survival time for patients receiving whole brain radiotherapy was about 3 to 6 months. Studies have shown that the incidence of brain metastasis is not only related to tumor size, N stage and tumor cell type, but also more likely to occur in NSCLC patients with sensitive gene mutation. With the rapid development of NSCLC molecular targeted therapy and precise radiotherapy, the new main therapeutic methods for NSCLC brain metastasis in recent years include stereotactic radiotherapy for (SRT),. Based on intensity modulated technique, simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain) and molecular targeted therapy were carried out. However, at present, the best treatment choice for NSCLC brain metastasis, especially for asymptomatic brain metastasis patients, is still controversial. The choice and combined application mode of individualized treatment for different patients is still a problem to be explored. Based on the synergistic effect of radiotherapy and molecular targeted therapy on the basis of cell and molecule, The purpose of this study was to prospectively compare the efficacy of radiotherapy combined with targeted therapy and targeted therapy alone in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutations, and subgroup analysis of different molecular targets and mutation sites. It is expected that this study will provide a basis for optimizing the curative effect of patients with NSCLC brain metastasis.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a randomized phase II clinical trial. The objective of the study is to assess efficacy and safety of brain radiotherapy combined with targeted therapy and simple targeted therapy in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutation. Patients were randomized with equal allocation to Molecular targeted therapy alone or with brain radiotherapy. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • The Second Afiliated Hospital of Nanchang University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histology confirmed that it was non-small cell lung cancer;
  • EGFR, ALK or ROS1 gene detection showed sensitive gene mutation, and patients were willing to receive targeted therapy;
  • brain MRI confirmed brain metastasis;
  • asymptomatic or symptomatic brain metastasis could be controlled by glucocorticoid;
  • PS score 0-1;
  • no brain radiotherapy or targeted therapy before entering the group;
  • there was no history of malignant tumor and no serious medical diseases;
  • Laboratory examination: White blood cell count ≥ 4 *10^9/L, neutrophil count ≥ 2.0 *10^9, platelet count ≥ 100 *10^9, hemoglobin ≥ 10 g / L, liver and kidney function and ECG were normal;
  • the pregnancy test was negative within 3 days before entering the group, and agreed to use medically effective contraceptives during the experiment;
  • sign informed consent form.

Exclusion Criteria:

  • Small cell lung cancer was confirmed by pathology;
  • other malignant tumors (unless PFS ≥ 3 years, except non-black skin cancer);
  • were treated with brain radiotherapy or targeted therapy before;
  • those with other potentially serious diseases (congestive heart failure, transmural myocardial infarction, admission with severe acute bacterial or fungal infection, COPD or other respiratory diseases that affect treatment, etc.), Taking into account that the study may exacerbate or fail to control the disease;
  • severe immunosuppressive diseases, such as AIDS;
  • pregnant women, lactating women or women of childbearing age who do not agree with the use of effective contraception in the trial;
  • Intracranial metastasis with obvious symptoms or symptoms that can not be relieved by glucocorticoid alone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: molecular targeted therapy group
Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)
Drug: molecular targeted therapies
if EGFR mutation is positive, (gefitinib, ecotinib, erlotinib）or ALK/ROS-1 positive（Crizotinib）
Other Names:
  • Targeted Therapy, Molecular
  • Therapy, Molecular Targeted
  • Targeted Molecular Therapies
Experimental: Brain Radiotherapy and molecular targeted therapy group
Brain Radiotherapy (stereotactic radiotherapy was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain )was used for more than 3 intracranial lesions);Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)
Drug: molecular targeted therapies
if EGFR mutation is positive, (gefitinib, ecotinib, erlotinib）or ALK/ROS-1 positive（Crizotinib）
Other Names:
  • Targeted Therapy, Molecular
  • Therapy, Molecular Targeted
  • Targeted Molecular Therapies
Radiation: Brain Radiotherapy
SRS was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain)was used for more than 3 intracranial lesions
Other Names:
  • Stereotactic radiotherapy,SRS
  • simultaneous modulated accelerated radiation therapy for Brain,SMART-Brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial progression-free survival,iPFS-LM
Time Frame: Every 6 weeks up to 2 years
Time from BM diagnosis to the first documentation of intracranial lesion progression or death with documented intracranial progression
Every 6 weeks up to 2 years
Objective Response Rate,ORR
Time Frame: 1 month after treatment
ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)
1 month after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
adverse events
Time Frame: Every 6 weeks up to 2 years
Number of patients with adverse events (AEs) as a measure of safety and tolerability
Every 6 weeks up to 2 years
Progress Free Survival rate,PFS
Time Frame: Every 6 weeks up to 2 years
The period from the start of treatment to the progression or death of a patient
Every 6 weeks up to 2 years
Median Survival Time,MST
Time Frame: Every 6 weeks up to 2 years
the cumulative survival rate is 0.5, the corresponding survival time means that only 50% of the individuals can live through this time.
Every 6 weeks up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival rate, OS
Time Frame: Every 6 weeks up to 2 years, and then every 3 months up to 5 years
time from the beginning of study to death due to any cause or last follow-up
Every 6 weeks up to 2 years, and then every 3 months up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Nanchang University

Collaborators

Nanchang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2019

Primary Completion (Anticipated)

December 30, 2021

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

November 13, 2019

First Submitted That Met QC Criteria

December 9, 2019

First Posted (Actual)

December 10, 2019

Study Record Updates

Last Update Posted (Actual)

December 10, 2019

Last Update Submitted That Met QC Criteria

December 9, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Y-Q201802-009

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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