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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital of Nanchang University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 10, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 10, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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