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

Sponsor

Second Affiliated Hospital of Nanchang University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04193007

Collaborator

Nanchang University (Other)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Brain Metastases	Drug: molecular targeted therapies Radiation: Brain Radiotherapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2019

Anticipated Primary Completion Date :

Dec 30, 2021

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Intracranial progression-free survival,iPFS-LM [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
Objective Response Rate,ORR [1 month after treatment]
ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)

Secondary Outcome Measures

Progress Free Survival rate,PFS [Every 6 weeks up to 2 years]
The period from the start of treatment to the progression or death of a patient
Median Survival Time,MST [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.
adverse events [Every 6 weeks up to 2 years]
Number of patients with adverse events (AEs) as a measure of safety and tolerability

Other Outcome Measures

Overall Survival rate, OS [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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