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

Phase 2

• Conditions: Non Small Cell Lung Cancer; Brain Metastases
• Interventions: Drug: molecular targeted therapies; Radiation: Brain Radiotherapy

• Registration Number: NCT04193007
• Lead Sponsor: Second Affiliated Hospital of Nanchang University

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.

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 Timeline

• Status Verified: 2019-11
• Study First Submitted: 2019-11-13
• Study Start: 2019-12-01
• Study First Submitted QC: 2019-12-09
• Last Update Submitted: 2019-12-09
• Study First Posted: 2019-12-10
• Last Update Posted: 2019-12-10
• Primary Completion: 2021-12-30
• Study Completion: 2022-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
molecular targeted therapy group	molecular targeted therapies	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)
Brain Radiotherapy and molecular targeted therapy group	molecular targeted therapies	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)
Brain Radiotherapy and molecular targeted therapy group	Brain Radiotherapy	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

The Second Afiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China