Leptomeningeal MetastasesPhase 1/2NCT05289908

Intrathecal Pemetrexed for Leptomeningeal Metastasis

A Phase 1/2 study testing Pemetrexed (1), Pemetrexed (2) and Folic Acid in people with Leptomeningeal Metastases, run by The First Hospital of Jilin University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Leptomeningeal Metastases
What is being tested?: Pemetrexed (1), Pemetrexed (2) and Folic Acid
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 1 siteChina
Study dates: 21 Feb 2022to 31 Mar 2024
Phase: Phase 1/2
Are there results?: None posted in the registry

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

Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid cytology or neuroimaging, or patients who got the clinical diagnosis by combining with the history of cancer, clinical manifestation, cerebrospinal fluid examination, neuroimaging etc.;
Patients who have been diagnosed as malignant solid tumor according histopathology or cytopathology combined with imaging;
No prior intrathecal chemotherapy;
Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3;
No other severe chronic diseases;
No history of severe nervous system disease;
No severe dyscrasia.

Who cannot join

Patients receiving molecularly targeted drugs that are effective in treating leptomeningeal metastases within 2 weeks prior to enrollment;
Patients with hydrocephalus or other factors suggestive of cerebrospinal fluid circulation obstruction;
patients with serious central nervous system disorders including severe encephalopathy, moderate or severe coma, and Glasgow Coma Score of <8 points;
Patients who have been diagnosed as hematological malignancy or primary central germ cell tumor;
Other reasons that were unsuitable for this study, including patients with lethal or extensive systemic diseases with few treatment options,psychiatric illness and poor compliance.

Trial locations and contacts

1 site in 1 country.

China1 site

The First Hospital of Jilin University
Changchun, Jilin, 130021

Other trials in China

About this study

Official title: Phase I/II Clinical Trial of Intrathecal Pemetrexed as First Line Intrathecal Chemotherapy in Patients With Leptomeningeal Metastasis

Intrathecal chemotherapy is one of the most important treatment modalities for leptomeningeal metastasis of solid tumors. In the previous study(Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastasis From Non-small Cell Lung Cancer: A Prospective Pilot Clinical Trial. ClinicalTrials.gov identification number: NCT03101579), pemetrexed presented feasibility of intrathecal administration. Pemetrexed at 10 mg dose level on the schedule of 1-2 times per week was recommended as an intrathecal administration agent for patients with refractory leptomeningeal metastases from non-small-cell lung cancer in the previous study. Moreover, the maximum-tolerated dose and recommended dose of intrathecal pemetrexed in the previous study was obtained without vitamin supplementation. Vitamin supplementation has been shown to reduce pemetrexed-induced myelosuppression. In this study, the regimen of intrathecal pemetrexed with folic acid and vitamin B12 supplementation may provide higher safety. Therefore, the purpose of this study is to investigate the maximally tolerated dose and evaluate the safety and effectiveness of intrathecal pemetrexed with vitamin supplementation as the first-line intrathecal chemotherapy in patients with leptomeningeal metastases from malignant solid tumors.

Read the detailed description

This is a phase I/II clinical trial. The objective of the study is patients with leptomeningeal metastases from solid tumors. Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. In phase I study, the initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg.... A minimum of three patients and a maximum of six are enrolled in each cohort. A dose-limiting toxicity is defined as grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity. If none of the three patients experiences any dose-limiting toxicity, the subsequent three patients are enrolled at the next higher dosage level. If one of three patients experiences a dose-limiting toxicity, up to three more patients are enrolled at the same level. The maximum-tolerated dose is defined as the dose where 0/3 or 1/6 patients experiences a dose-limiting toxicity with at least two patients encountering dose-limiting toxicity at the higher dose. If more than two patients experience a dose-limiting toxicity, that level is considered too toxic. The maximum-tolerated dose is exceeded and an additional three patients should be treated at the next lower dose level. Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed. A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks. In phase II study, the maximum-tolerated dose determined in phase I study is chosen.

Conditions: Leptomeningeal Metastases
Being tested: Pemetrexed (1), Pemetrexed (2), Folic Acid, Vitamin B12, Dexamethasone
Keywords: Leptomeningeal metastasis, Intrathecal chemotherapy, 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.

Pemetrexed (1)Drug
Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg....
Pemetrexed (2)Drug
The maximum-tolerated dose determined in phase I study is chosen as the treatment dose in phase II study.
Folic AcidDrug
Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed.
Vitamin B12Drug
A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks.
DexamethasoneDrug
Dexamethasone, 5 mg, intrathecal injection via lumbar puncture, simultaneously with pemetrexed, twice per week for 2 weeks, followed by once per week for 2-4 weeks.

Study groups in NCT05289908
Study group	Role	What they receive
Phase I study	Experimental	Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg.... A minimum of three patients and a maximum of six are enrolled in each cohort. Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed. A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks. Receives: Drug: Pemetrexed (1); Drug: Folic Acid; Drug: Vitamin B12; Drug: Dexamethasone
Phase II study	Experimental	Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. The maximum-tolerated dose determined in phase I study is chosen as the treatment dose in phase II study. Receives: Drug: Pemetrexed (2); Drug: Folic Acid; Drug: Vitamin B12; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximal tolerated dose
A dose-limiting toxicity (DLT) was defined as grade 3 neurological toxicities (e.g. chemical meningitis) or other grade 4 toxicity. If more than two patients experienced a DLT, that level was considered too toxic. The maximal tolerated dose (MTD) was exceeded and an additional three patients should be treated at the next lower dose level. The MTD was defined as the dose where 0/3 or 1/6 patients experienced a DLT with at least two patients encountering DLT at the higher dose.
Measured: From the beginning of the treatment until two months after the treatment.
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, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.
Measured: From the beginning of the treatment until two months after the treatment.

Secondary outcomes (1)

Overall survival time
Survival time was defined from the enrollment until death or the last follow-up.
Measured: The evaluation was performed at least 7 months after leptomeningeal metastasis diagnosis or until death.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Feb 202231 Mar 2024

First posted22 Mar 2022
Study start21 Feb 2022
Primary completion20 Mar 2023
Study completion31 Mar 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Leptomeningeal MetastasesStudies of the same condition, open and under way.
More trials run by The First Hospital of Jilin UniversityThe sponsor's other registered studies.
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: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05289908
Sponsor's protocol ID: PMLM
Status last verified: Nov 2024
First submitted: 10 Mar 2022
Last updated: 4 May 2025
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

Pan Z, Yang G, He H, Cui J, Li W, Yuan T, Chen K, Jiang T, Gao P, Sun Y, Cong X, Li Z, Wang Y, Pang X, Song Y, Zhao G. Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study. Ther Adv Med Oncol. 2020 Jul 17;12:1758835920937953. doi: 10.1177/1758835920937953. eCollection 2020.
PubMed 32733606
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.
PubMed 31544065
Pan Z, Ye X, Huang Y, Tai P, Liu M, Sun X, Tang R, Gu A, Wang Z, Shen L, Pang X, Yuan T, Yang G. Intrathecal pemetrexed for newly diagnosed leptomeningeal metastases: a multicenter, open-label, phase I/II study. J Neurooncol. 2025 Nov;175(2):857-868. doi: 10.1007/s11060-025-05160-4. Epub 2025 Jul 23.
PubMed 40699526

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis
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All Leptomeningeal Metastases trials

Study at a glance

From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Clinical Trial of Intrathecal Pemetrexed as First Line Intrathecal Chemotherapy in Patients With Leptomeningeal Metastasis
ClinicalTrials.gov ID: NCT05289908
Acronym / sponsor ID: PMLM
Conditions: Leptomeningeal Metastases
Keywords: Leptomeningeal metastasis, Intrathecal chemotherapy, Pemetrexed
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: The First Hospital of Jilin UniversityUniversity, hospital or other
Collaborators: Affiliated Hospital of Guangdong Medical University, Second Affiliated Hospital of Guangzhou Medical University, Guangdong 999 Brain Hospital, The Second Hospital of Hebei Medical University, Panjin Liaoyou Gem Flower Hospital, Wuxi People's Hospital, Huizhou Third People's Hospital, Guangzhou Medical University
Study start: 21 Feb 2022 (actual)
Primary completion: 20 Mar 2023 (actual)
Study completion: 31 Mar 2024 (actual)
First posted: 22 Mar 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Phase I study	Experimental	Drug: Pemetrexed (1), Drug: Folic Acid, Drug: Vitamin B12, Drug: DexamethasonePemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg.... A minimum of three patients and a maximum of six are enrolled in each cohort. Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed. A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks.
Phase II study	Experimental	Drug: Pemetrexed (2), Drug: Folic Acid, Drug: Vitamin B12, Drug: DexamethasonePemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. The maximum-tolerated dose determined in phase I study is chosen as the treatment dose in phase II study.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid cytology or neuroimaging, or patients who got the clinical diagnosis by combining with the history of cancer, clinical manifestation, cerebrospinal fluid examination, neuroimaging etc.;
Patients who have been diagnosed as malignant solid tumor according histopathology or cytopathology combined with imaging;
No prior intrathecal chemotherapy;
Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3;
No other severe chronic diseases;

Key exclusion criteria (5 listed)

Patients receiving molecularly targeted drugs that are effective in treating leptomeningeal metastases within 2 weeks prior to enrollment;
Patients with hydrocephalus or other factors suggestive of cerebrospinal fluid circulation obstruction;
patients with serious central nervous system disorders including severe encephalopathy, moderate or severe coma, and Glasgow Coma Score of <8 points;
Patients who have been diagnosed as hematological malignancy or primary central germ cell tumor;
Other reasons that were unsuitable for this study, including patients with lethal or extensive systemic diseases with few treatment options,psychiatric illness and poor compliance.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pemetrexed (1)Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg....	Drug	Phase I study
Pemetrexed (2)The maximum-tolerated dose determined in phase I study is chosen as the treatment dose in phase II study.	Drug	Phase II study
Folic AcidFolic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed.	Drug	Phase I study, Phase II study
Vitamin B12A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks.	Drug	Phase I study, Phase II study
DexamethasoneDexamethasone, 5 mg, intrathecal injection via lumbar puncture, simultaneously with pemetrexed, twice per week for 2 weeks, followed by once per week for 2-4 weeks.	Drug	Phase I study, Phase II study

Primary outcome

Maximal tolerated dose
Time frame: From the beginning of the treatment until two months after the treatment.
A dose-limiting toxicity (DLT) was defined as grade 3 neurological toxicities (e.g. chemical meningitis) or other grade 4 toxicity. If more than two patients experienced a DLT, that level was considered too toxic. The maximal tolerated dose (MTD) was exceeded and an additional three patients should be treated at the next lower dose level. The MTD was defined as the dose where 0/3 or 1/6 patients experienced a DLT with at least two patients encountering DLT at the higher dose.
Incidence of treatment-related adverse events
Time frame: From the beginning of the treatment until two months after the treatment.
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, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.

1 secondary outcome

Overall survival time
Time frame: The evaluation was performed at least 7 months after leptomeningeal metastasis diagnosis or until death.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
Background: PubMed 32733606Pan Z, Yang G, He H, Cui J, Li W, Yuan T, Chen K, Jiang T, Gao P, Sun Y, Cong X, Li Z, Wang Y, Pang X, Song Y, Zhao G. Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study. Ther Adv Med Oncol. 2020 Jul 17;12:1758835920937953. doi: 10.1177/1758835920937953. eCollection 2020.
Background: PubMed 31544065Pan 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.
Derived from this study: PubMed 40699526Pan Z, Ye X, Huang Y, Tai P, Liu M, Sun X, Tang R, Gu A, Wang Z, Shen L, Pang X, Yuan T, Yang G. Intrathecal pemetrexed for newly diagnosed leptomeningeal metastases: a multicenter, open-label, phase I/II study. J Neurooncol. 2025 Nov;175(2):857-868. doi: 10.1007/s11060-025-05160-4. Epub 2025 Jul 23.
Individual participant dataSharing planned: Yes. All individual participant data that underlie results in a publication will be available to other researchers.

Related trials for Leptomeningeal Metastases

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Multiple Dose Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases
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SERS-Based Diagnosis of Leptomeningeal Metastasis in EGFR-Mutant NSCLC
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Zhenyu Pan principal investigator

The First Hospital of Jilin University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pemetrexed (1), Pemetrexed (2) and Folic Acid in people with Leptomeningeal Metastases, run by The First Hospital of Jilin University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (time frame: From the beginning of the treatment until two months after the treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05289908, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.