Leptomeningeal MetastasisPhase 1/2NCT06462222
Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors
A Phase 1/2 study testing Toripalimab, pemetrexed in people with Leptomeningeal Metastasis, run by Guangzhou Medical University at 5 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leptomeningeal Metastasis
- What is being tested?
- Toripalimab, pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 5 sitesChina
- Study dates
- 30 Jun 2024to Nov 2026
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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, active 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Beijing Chest Hospital, Capital Medical University
Beijing, 101100
Cancer Center, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine
Beijing
The Affiliated Huizhou Hospital, Guangzhou Medical University
Huizhou, Guangdong, 516000
Huizhou First Hospital Affiliated to Guangdong Medical University
Huizhou, Guangdong
Jinshan Hospital, Fudan University
Shanghai
About this study
Official title: Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors: a Phase I/II Study
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.
Read the 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.
- Conditions
- Leptomeningeal Metastasis
- Being tested
- Toripalimab, pemetrexed
- Keywords
- Leptomeningeal metastasis, Intrathecal chemotherapy, Immune checkpoint inhibitor, Pemetrexed
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Toripalimab, pemetrexedDrug
Drug 1: Toripalimab 40 mg; Drug 2: pemetrexed 15mg. intrathecal injection therapy
| Study group | Role | What they receive |
|---|---|---|
| Group | Experimental | Immune checkpoint inhibitor combined with pemetrexed Receives: Drug: Toripalimab, pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The dose limiting toxicity will be evaluated during the first 6 weeks of study treatment (the DLT window).
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.
Measured: From date of treatment until discontinuation of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2024
- Study start30 Jun 2024
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guangzhou Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Jinshan Hospital Fudan University
- Responsible party
- Principal investigator, Zhenyu Pan, Jinshan Hospital Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06462222
- Sponsor's protocol ID
- TPLM
- Status last verified
- May 2026
- First submitted
- 12 Jun 2024
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data that underlie results in a publication will be available to other researchers.
Publications
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.
PubMed 36997799Pan 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.
PubMed 31544065