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

Leptomeningeal Metastasis Clinical Trial

Official title:

Immune Checkpoint Inhibitor Combined With Pemetrexed Intrathecal Injection for Leptomeningeal Metastasis From Solid Tumors： a Phase I/II Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462222
• Other study ID #: 2024-KY-029-01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 20, 2024
• Est. completion date: June 20, 2026

Study information

• Verified date: June 2024
• Source: Guangzhou Medical University
• Contact: Zhenyu Pan
• Phone: +8618718178286
• Email: dr-zypan[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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, to evaluate the safety and efficacy.

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 endpoint of the phase I study was to determine the recommended phase II dose (PR2D). The primary endpoint of the Phase II study was to assess the safety and clinical response rate of immune checkpoint inhibitor in combination with pemetrexed intrathecally under PR2D, with secondary endpoints of overall survival, and neurological progression-free survival.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 34
• Est. completion date: June 20, 2026
• Est. primary completion date: April 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leptomeningeal Metastasis
• Meningeal Carcinomatosis
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
China	Guangzhou Medical University	Huizhou

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Medical University

Country where clinical trial is conducted

China, 

References & 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. Erratum In: Nat Med. 2024 Apr 22. doi: 10.1038/s41591-024-02998-5. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PR2D	The recommended phase II dose. 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.]
Primary	Clinical response rate	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.	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.
Primary	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.
Secondary	Neurological progression-free survival (NPFS)	NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.	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.
Secondary	Overall survival(OS)	Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.	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).