Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors: a Phase I/II Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 45
- Locations
- 5
- Primary Endpoint
- Recommended dose
Study Overview
Brief Summary
This is an open-label, single-arm, phase I/II trial of immune checkpoint inhibitor combined with pemetrexed intrathecal injection for leptomeningeal metastasis from solid tumors.
Detailed Description
This is an open-label, single-arm, phase I/II trial of immune checkpoint inhibitor combined with pemetrexed intrathecal injection for leptomeningeal metastasis from solid tumors. The primary objective was to assess recommended dose and safety based on adverse events (AEs). All participants were observed to evaluate the clinical response rate (CRR), disease control rate (DCR) and overall survival (OS). Patients underwent cerebrospinal fluid (CSF) and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
- •Male or female aged between 18 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm
- •No history of severe nervous system disease; No severe dyscrasia.
Exclusion Criteria
- •Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than
- •Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
- •A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing >Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.
- •Patients with poor compliance or other reasons that were unsuitable for this study.
Arms & Interventions
Group
Immune checkpoint inhibitor combined with pemetrexed
Intervention: Toripalimab, pemetrexed (Drug)
Outcomes
Primary Outcomes
Recommended dose
Time Frame: 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 recommended dose of intrathecal PD-1 inhibitor. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.
Incidence of treatment-related adverse events
Time Frame: 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. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events.
Secondary Outcomes
No secondary outcomes reported
Investigators
Zhenyu Pan
Professor
Guangzhou Medical University