Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors

NCT06462222 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: TPLM
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Leptomeningeal Metastasis

Keywords

Leptomeningeal metastasis; Intrathecal chemotherapy; Immune checkpoint inhibitor; Pemetrexed

Outcome Measures

Primary Outcomes (2)

• Recommended dose

  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.

  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.]

• Incidence of treatment-related adverse events

  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.

  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.

Other Outcomes (3)

• 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.

• Progression-free survival related to leptomeningeal metastasis (LMPFS)

  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.

• Overall survival(OS)

  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).

Study Arms (1)

Group

EXPERIMENTAL

Immune checkpoint inhibitor combined with pemetrexed

Drug: Toripalimab, pemetrexed

Interventions

Toripalimab, pemetrexed DRUG

Drug 1: Toripalimab 40 mg; Drug 2: pemetrexed 15mg. intrathecal injection therapy

Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/mm3.
• No history of severe nervous system disease; No severe dyscrasia.

You may not qualify if:

• Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
• 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.

Sponsors & Collaborators

• Guangzhou Medical University: lead

Study Sites (1)

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou, Guangdong, 516000, China

Location

Related Publications (2)

• 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.

  PMID: 36997799 BACKGROUND

• 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.

  PMID: 31544065 BACKGROUND

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

toripalimab; Pemetrexed

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: June 17, 2024
• Study Start: June 30, 2024
• Primary Completion: January 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Starting 6 months after publication
• Access Criteria: Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete

Locations

CN (1)