Clinical trial NCT06462222: Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors
Official title: Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors: a Phase I/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leptomeningeal Metastasis
Keywords: Leptomeningeal metastasis
Intrathecal chemotherapy
Immune checkpoint inhibitor
Pemetrexed
Lead sponsor: Guangzhou Medical University
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.
2. Male or female aged between 18 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
3. No history of severe nervous system disease; 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. 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.
4. Patients with poor compliance or other reasons that were unsuitable for this study.

Primary outcomes:
measure: Recommended dose
timeFrame: 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.]
measure: Incidence of treatment-related adverse events
timeFrame: 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.
Secondary outcomes:
Other outcomes:
measure: Clinical response rate
timeFrame: 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.
measure: Progression-free survival related to leptomeningeal metastasis (LMPFS)
timeFrame: From date of treatment until the date of first documented leptomeningeal metastasis progression or date of death from any cause, whichever came first, assessed up to 6 months.
measure: Overall survival(OS)
timeFrame: From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).
Locations:
city: Huizhou
country: China
facility: The Affiliated Huizhou Hospital, Guangzhou Medical University
state: Guangdong
Study officials:
References:
citation: Glitza Oliva IC, Ferguson SD, Bassett R Jr, Foster AP, John I, Hennegan TD, Rohlfs M, Richard J, Iqbal M, Dett T, Lacey C, Jackson N, Rodgers T, Phillips S, Duncan S, Haydu L, Lin R, Amaria RN, Wong MK, Diab A, Yee C, Patel SP, McQuade JL, Fischer GM, McCutcheon IE, O'Brien BJ, Tummala S, Debnam M, Guha-Thakurta N, Wargo JA, Carapeto FCL, Hudgens CW, Huse JT, Tetzlaff MT, Burton EM, Tawbi HA, Davies MA. Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results. Nat Med. 2023 Apr;29(4):898-905. doi: 10.1038/s41591-022-02170-x. Epub 2023 Mar 30.
citation: Pan Z, Yang G, Cui J, Li W, Li Y, Gao P, Jiang T, Sun Y, Dong L, Song Y, Zhao G. A Pilot Phase 1 Study of Intrathecal Pemetrexed for Refractory Leptomeningeal Metastases From Non-small-cell Lung Cancer. Front Oncol. 2019 Aug 30;9:838. doi: 10.3389/fonc.2019.00838. eCollection 2019.