Leptomeningeal Metastases
Conditions
Keywords
Leptomeningeal Metastases, EGFR, Pemetrexed, intrathecal injection, vometinib
Brief summary
With the rapid development of targeted drugs, the treatment of patients with leptomeningeal metastasis has become a very difficult problem in clinical work. High-dose targeted drugs and intrathecal chemotherapy are important treatment methods for meningeal metastasis. However, it is vital to note that safety is also of concern in previous studies of intrathecal chemotherapy. In this study, we aim to evaluate the safety and effectiveness of patient using chemo-holiday therapy based on the cerebrospinal fluid cytology, combined with double-dose EGFR-targeted drug in patients with leptomeningeal metastases from EGFR-positive NSCLC.
Detailed description
This is a single arm phase II clinical trial. The objective of the study is patients with leptomeningeal metastases from non-small cell lung cancer after EGFR TKIs treatment. The pemetrexed is administrated by intrathecal injection with a dose of 50mg, once per week for 4 weeks, followed by every four weeks thereafter. The cerebrospinal fluid(CSF) samples are collected every 4 weeks and the cytology examination will be performed. If CSF cytology was negative, CSF cytology was tested again 1 week later. Two negative tests were considered as negative CSF cytology. If the cytology of cerebrospinal fluid was negative after 4 consecutive intrathecal injections, the intrathecal injection should be stopped. If positive, continue to give a intrathecal injection every 4 weeks until CSF cytology is negative. If CSF cytological positivity or worsening of neurological symptoms occurs again during discontinuation, or if new symptoms appear, the intrathecal injection should be resumed every 4 weeks. in the meantime, double dose of vometinib (160mg) is given.
Interventions
DRUGpemetrexed
The pemetrexed is administrated by intrathecal injection with a dose of 50mg, once per week for 4 weeks, followed by every four weeks thereafter. The cerebrospinal fluid(CSF) samples are collected every 4 weeks and the cytology examination will be performed. If CSF cytology was negative, CSF cytology was tested again 1 week later. Two negative tests were considered as negative CSF cytology. If the cytology of cerebrospinal fluid was negative after 4 consecutive intrathecal injections, the intrathecal injection should be stopped. If positive, continue to give a intrathecal injection every 4 weeks until CSF cytology is negative. If CSF cytological positivity or worsening of neurological symptoms occurs again during discontinuation, or if new symptoms appear, the intrathecal injection should be resumed every 4 weeks.
DRUGvometinib
double dose of vometinib (160mg)
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged between 18 and 75 years. 2. Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations. 3. Cytologically confirmed diagnosis of leptomeningeal metastasis. 4. Normal organ function. 5. No history of severe nervous system disease. 6. No severe dyscrasia.
Exclusion criteria
1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11. 2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment. 3. Patients with poor compliance or other reasons that were unsuitable for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From the enrollment of this study until date of death from any cause, up to a maximum of approximately 2 years | Overall survival is the time from the date of enrollment of this study to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact on quality of life | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months. | Impact on quality of life using QLQ-C30 (V3.0) |
| Clinical response rate | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months. | The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study. |
| leptomeningeal metastases related progression-free survival | From date of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months. | The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol. |
| CSF cytological clearance | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months. | The cerebrospinal fluid samples are collected every 4 weeks and the cytology examination will be performed. |
| Adverse events | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months. | The incidence of treatment-related adverse events were measured for determining tolerability and safety according to Common Toxicity Criteria Adverse Event (CTCAE), version 5.0. |
Countries
China
Contacts
Primary ContactDepartment of Thoracic Oncology, Zhejiang Cancer Hospital
Outcome results
None listed