Non-small Cell Lung Cancer Clinical Trial
Official title:
The Efficacy and Safety of Aumolertinib Combined Ommaya Reservoir Intrathecal Chemotherapy With Pemetrexed for Leptomeningeal Metastasis From EGFR-mutated NSCLC and Investigate the Efficacy Prognostic Value of Dynamic Changes of cfDNA
This is a prospective, open-label, single-arm clinical trial. The aim of this study is to evaluate the efficacy and safety of almonertinib and intrathecal chemotherapy in patients with advanced EGFR mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) and leptomeningeal metastasis, and to explore the predictive value of dynamic changes of cfDNA in cerebrospinal fluid for efficacy and prognosis. A total of 40 subjects who met the inclusion criteria were enrolled in the study and received almonertinib (165mg, oral, once a day) combined with intrathecal infusion. Before and after treatment, cerebrospinal fluid was extracted for cfDNA detection by a 49 gene detection panel. Treatment continued until disease progression or other discontinuation criteria were met. In addition, the subjects received regular hematological and imaging examinations to evaluate the condition. Finally, through data analysis, the progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), duration of response (DoR), and overall survival (OS) of patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastasis who received almonertinib combined with intrathecal infusion chemotherapy were evaluated. The dynamic changes of cfDNA in cerebrospinal fluid before and after treatment were explored and the correlation between the dynamic changes of cfDNA in cerebrospinal fluid and the therapeutic effect was explored.
This study is a prospective, open-label, single-arm clinical trial to explore the efficacy and safety of almonertinib and intrathecal chemotherapy in patients with advanced NSCLC and leptomeningeal metastasis and the predictive value of cfDNA changes for efficacy and prognosis. A total of 40 patients aged 18 years or older with confirmed advanced NSCLC with leptomeningeal metastases and an EGFR sensitive mutation (exon 19 deletion or 21 L858R) are expected to be enrolled. The intervention was almonertinib (165mg orally, once daily) combined with intrathecal infusion therapy (pemetrexed 30 mg by injection on days 1 and 8 of each cycle). Treatment continued until disease progression or other discontinuation criteria were met. Relevant examinations and data collection during the study were as follows. CSF collection: Approximately 15mL of CSF was collected from each sample, and sampling was performed before C1D1 administration and within one week after PD (24 hours after the previous day's administration). Venous blood sample collection: subjects who underwent CSF sampling were performed before C1D1 and C2D1 administration (24 hours after the previous day's dose) and within 1 week after PD. Before treatment, all enrolled patients underwent neurological examination, complete blood count, serum biochemistry, coagulation indexes, blood tumor markers, cytological and CSF tumor markers, electrocardiogram, brain and spinal cord MRI, chest and abdominal CT, and bone scan. The blood and CSF tests described above were performed for each treatment cycle. Imaging was performed every 2 months or if clinical progression was suspected until death. Before each intrathecal infusion, LM-related neurological symptoms, PS score, Neuro-oncology Working Group (RANO) score, and headache score were assessed and recorded in detail. Adverse events (AEs) were graded and recorded according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). The primary objective was to evaluate the progression-free survival (PFS) of almonertinib versus intrathecal chemotherapy in patients with advanced EGFR mutation-positive NSCLC and leptomeningeal metastases. The secondary study objectives were: first, to evaluate the efficacy of almonertinib and intrathecal chemotherapy in the treatment of advanced NSCLC with leptomeningeal metastases: disease control rate (DCR), objective response rate (ORR), duration of response (DoR), and overall survival (OS); Intracranial: intracranial progression-free survival (iPFS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and intracranial duration of response (iDoR). Second, evaluate the time to symptom improvement of almonertinib versus intrathecal chemotherapy in patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastases. Third, we evaluated the safety of almonertinib and intrathecal infusion chemotherapy in patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastases. The objectives of this pilot study were as follows: 1) To evaluate the correlation between baseline and post-treatment cfDNA changes in CSF and treatment response; Second, the correlation between baseline CSF cfDNA status and patient prognosis; Third, sensitivity analysis based on baseline CSF cfDNA mutations and leptomeningeal metastases after targeted therapy. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT03087448 -
Ceritinib + Trametinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC)
|
Phase 1 | |
Recruiting |
NCT05042375 -
A Trial of Camrelizumab Combined With Famitinib Malate in Treatment Naïve Subjects With PD-L1-Positive Recurrent or Metastatic Non-Small Cell Lung Cancer
|
Phase 3 | |
Completed |
NCT02526017 -
Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
|
Phase 1 | |
Enrolling by invitation |
NCT00068003 -
Harvesting Cells for Experimental Cancer Treatments
|
||
Terminated |
NCT05414123 -
A Therapy Treatment Response Trial in Patients With Leptomeningeal Metastases ((LM) Using CNSide
|
||
Recruiting |
NCT05059444 -
ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
|
||
Recruiting |
NCT05919537 -
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
|
Phase 1 | |
Recruiting |
NCT05009836 -
Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Active, not recruiting |
NCT03170960 -
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT03219970 -
Efficacy and Safety of Osimertinib for HK Chinese With Metastatic T790M Mutated NSCLC-real World Setting.
|
||
Recruiting |
NCT05949619 -
A Study of BL-M02D1 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer or Other Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT04054531 -
Study of KN046 With Chemotherapy in First Line Advanced NSCLC
|
Phase 2 | |
Withdrawn |
NCT03519958 -
Epidermal Growth Factor Receptor (EGFR) T790M Mutation Testing Practices in Hong Kong
|
||
Completed |
NCT03384511 -
The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
|
Phase 4 | |
Terminated |
NCT02580708 -
Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT01871805 -
A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)
|
Phase 1/Phase 2 | |
Terminated |
NCT04042480 -
A Study of SGN-CD228A in Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05919641 -
LIVELUNG - Impact of CGA in Patients Diagnosed With Localized NSCLC Treated With SBRT
|
||
Completed |
NCT03656705 -
CCCR-NK92 Cells Immunotherapy for Non-small Cell Lung Carcinoma
|
Phase 1 |