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

Non Small Cell Lung Cancer Clinical Trial

— BRATR  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04193007
• Other study ID #: Y-Q201802-009
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 1, 2019
• Est. completion date: June 1, 2022

Study information

• Verified date: November 2019
• Source: Second Affiliated Hospital of Nanchang University
• Contact: Liu Anwen, Phd
• Phone: +8613767120022
• Email: awliu666[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 1, 2022
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Non Small Cell Lung Cancer

Intervention

Drug:
• molecular targeted therapies
if EGFR mutation is positive, (gefitinib, ecotinib, erlotinib)or ALK/ROS-1 positive(Crizotinib)

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

Locations

Country	Name	City	State
China	The Second Afiliated Hospital of Nanchang University	Nanchang	Jiangxi

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Nanchang University	Nanchang University

Country where clinical trial is conducted

China, 

References & Publications (17)

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* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival rate, OS	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
Primary	Intracranial progression-free survival,iPFS-LM	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
Primary	Objective Response Rate,ORR	ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)	1 month after treatment
Secondary	Progress Free Survival rate,PFS	The period from the start of treatment to the progression or death of a patient	Every 6 weeks up to 2 years
Secondary	Median Survival Time,MST	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
Secondary	adverse events	Number of patients with adverse events (AEs) as a measure of safety and tolerability	Every 6 weeks up to 2 years