Leptomeningeal MetastasisPhase 2NCT06901817
A Study of the Safety and Efficacy of Pemetrexed Combined with Nivolumab Via Intraventricular Injection for the Treatment of Refractory Non-squamous Non-small Cell Lung Cancer with Leptomeningeal Metastases
A Phase 2 study testing Intraventricular Pemetrexed, Intraventricular Nivolumab and Intraventricular Dexamethasone in people with Leptomeningeal Metastasis, run by Shanghai Cancer Hospital, China at 1 site in China.
Trial summary
The goal of this clinical trial is to learn if the intraventricular injection of Pemetrexed and Nivolumab works to treat refractory non-squamous non-small cell lung cancer with leptomeningeal metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastasis
- What is being tested?
- Intraventricular Pemetrexed, Intraventricular Nivolumab and Intraventricular Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2025to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who sign the informed consent form and are willing to complete the study according to the protocol;
- Patients must have radiographic and/or cerebrospinal fluid cytology evidence of leptomeningeal disease (LMD). The diagnosis of non-small cell lung cancer must be confirmed, based on histological and/or cytological diagnosis.
- Patients must have an ECOG performance status score of ≤ 2.
- Patients may use steroids to control symptoms related to the central nervous system, but the dose must be ≤ 4 mg of dexamethasone (or equivalent dose) within 24 hours. The patient's neurological symptoms should remain stable for at least 7 days, or they are reducing the dose of steroids. Physiological replacement doses for adrenal insufficiency are allowed.
- Patients who have received brain and/or spinal radiotherapy, including whole-brain radiation, stereotactic radiosurgery, or SBRT, can be enrolled, but must have completed radiation therapy at least 7 days before starting treatment.
- Patients who have received approved systemic treatments may continue the systemic treatment chosen by the researcher. Concurrent use of other drugs for intrathecal treatment is not allowed. For patients who have received other systemic treatments, the minimum washout periods are as follows:
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- Patients who have received intrathecal treatment must have had their last treatment at least 7 days before starting the study treatment.
- Patients who have received systemic chemotherapy must have had their last treatment at least 14 days before starting the study treatment.
- Patients who have received approved systemic immunotherapy (such as anti-PD-1, anti-CTLA4) must have had their last treatment at least 2 weeks before starting the study treatment.
- Patients who have received any other investigational drugs must have had their last treatment at least 14 days before starting the study treatment.
- Age ≥ 18 years.
- Able to provide written informed consent, including compliance with the requirements and restrictions listed in the consent form.
- Patients must have the organ and bone marrow function defined in Table 1 below.
- No contraindications to the installation of an Ommaya reservoir.
- Criteria for refractory leptomeningeal metastasis:
- Failed first- or second-generation TKI treatment, T790M mutation-negative;
- Failed third-generation TKI treatment;
- EGFR gene mutation-negative, failed first-line treatment.
Who cannot join
- Patients who require a VP shunt due to increased intracranial pressure.
- Patients must not have active autoimmune diseases requiring systemic treatment in the past two years (i.e., using disease-modifying agents, corticosteroids, or immunosuppressive drugs). Alternative therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered forms of systemic treatment.
- Subjects who need systemic treatment within 14 days prior to administration of the study drug, including the use of corticosteroids (>4 mg daily dexamethasone equivalent dose) or other immunosuppressive drugs. Inhaled or topical steroids and adrenal replacement therapy at a daily replacement dose >10 mg prednisone equivalent are allowed in the absence of active autoimmune diseases.
- Patients who have previously received PD-1 and/or anti-CTLA-4 therapy are eligible, unless they are experiencing > grade 2 side effects from such treatments. Ongoing physiological replacement doses for adrenal and thyroid insufficiency are allowed in the protocol.
- Patients currently receiving experimental anti-cancer drugs (co-treatment with approved targeted therapies is permitted).
- Patients with a history of other malignancies are eligible if they have appropriately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancers with no evidence of disease for more than 5 years.
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- Participation in another clinical trial within 30 days prior to randomization, receiving investigational drugs and any concomitant treatments containing investigational drugs.
- Immunodeficiency, HIV infection;
- Severe dysfunction of the heart, lungs, liver, or kidneys;
- Uncontrolled infection or active infection;
- Pregnant or breastfeeding women.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jiayan Chen, M.D. contact
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Min Fan, MD, 8618121299483, fanmin@fudan.edu.cn
About this study
Official title: A Multicenter, Prospective, Phase II Study on Intraventricular Injection of Pemetrexed Combined with Nivolumab Via an Ommaya Reservoir for the Treatment of Refractory Non-squamous Non-small Cell Lung Cancer (NSCLC) with Leptomeningeal Metastases in Previously Treated Patients
The goal of this clinical trial is to learn if the intraventricular injection of Pemetrexed and Nivolumab works to treat refractory non-squamous non-small cell lung cancer with leptomeningeal metastases. The main questions to answer are:
- Is the combination of Pemetrexed and Nivolumab safe to inject?
- How effective is the combination in disease control?
Read more
Participants will：
- Intrathecal injection of 30 mg pemetrexed via Ommaya reservoir, once every 4 weeks until disease progression;
- Intrathecal injection of 40 mg nivolumab via Ommaya reservoir, once every 4 weeks until disease progression;
- Before each intrathecal administration, a preliminary intrathecal injection of dexamethasone, 5 mg/2 mL, is given.
- Conditions
- Leptomeningeal Metastasis
- Being tested
- Intraventricular Pemetrexed, Intraventricular Nivolumab, Intraventricular Dexamethasone
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraventricular PemetrexedDrug
Intraventricular injection of 30 mg pemetrexed via Ommaya reservoir, once every 4 weeks until disease progression.
Intraventricular NivolumabDrug
Intraventricular injection of 40 mg nivolumab via Ommaya reservoir, once every 4 weeks until disease progression.
Intraventricular DexamethasoneDrug
Intraventricular injection of 5mg/2ml pemetrexed via Ommaya reservoir before injection of pemetrexed and nivolumab.
| Study group | Role | What they receive |
|---|---|---|
| Intraventricular Pemetrexed combined with Nivolumab | Experimental | Patients with leptomeningeal metastases from refractory non-squamous non-small cell lung cancer will receive Pemetrexed and Nivolumab vis Ommaya reservoir. Receives: Drug: Intraventricular Pemetrexed; Drug: Intraventricular Nivolumab; Drug: Intraventricular Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Event
Per CTCAE version 4.0
Measured: 30 days
Secondary outcomes (1)
objective response rate (ORR)
LM objective response rate (ORR) is defined as the proportion of patients with at least one objective response in LM, using a combined approach taking into account radiographic, neurologic and cytologic assessments based on RANO-LM.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2025
- Study start1 Mar 2025
- Primary completionNov 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 97 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Cancer Hospital, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fan Min, Shanghai Cancer Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06901817
- Sponsor's protocol ID
- FUSCC20240710
- Status last verified
- Mar 2025
- First submitted
- 24 Mar 2025
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Prospective, Phase II Study on Intraventricular Injection of Pemetrexed Combined with Nivolumab Via an Ommaya Reservoir for the Treatment of Refractory Non-squamous Non-small Cell Lung Cancer (NSCLC) with Leptomeningeal Metastases in Previously Treated Patients
- ClinicalTrials.gov ID
- NCT06901817
- Acronym / sponsor ID
- FUSCC20240710
- Conditions
- Leptomeningeal Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 97 participants (estimated)
- Lead sponsor
- Shanghai Cancer Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 30 Mar 2025 (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.
The goal of this clinical trial is to learn if the intraventricular injection of Pemetrexed and Nivolumab works to treat refractory non-squamous non-small cell lung cancer with leptomeningeal metastases. The main questions to answer are:
- Is the combination of Pemetrexed and Nivolumab safe to inject?
- How effective is the combination in disease control?
Participants will：
- Intrathecal injection of 30 mg pemetrexed via Ommaya reservoir, once every 4 weeks until disease progression;
- Intrathecal injection of 40 mg nivolumab via Ommaya reservoir, once every 4 weeks until disease progression;
- Before each intrathecal administration, a preliminary intrathecal injection of dexamethasone, 5 mg/2 mL, is given.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intraventricular Pemetrexed combined with Nivolumab | Experimental | Drug: Intraventricular Pemetrexed, Drug: Intraventricular Nivolumab, Drug: Intraventricular DexamethasonePatients with leptomeningeal metastases from refractory non-squamous non-small cell lung cancer will receive Pemetrexed and Nivolumab vis Ommaya reservoir. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients who sign the informed consent form and are willing to complete the study according to the protocol;
- Patients must have radiographic and/or cerebrospinal fluid cytology evidence of leptomeningeal disease (LMD). The diagnosis of non-small cell lung cancer must be confirmed, based on histological and/or cytological diagnosis.
- Patients must have an ECOG performance status score of ≤ 2.
- Patients may use steroids to control symptoms related to the central nervous system, but the dose must be ≤ 4 mg of dexamethasone (or equivalent dose) within 24 hours. The patient's neurological symptoms should remain stable for at least 7 days, or they are reducing the dose of steroids. Physiological replacement doses for adrenal insufficiency are allowed.
- Patients who have received brain and/or spinal radiotherapy, including whole-brain radiation, stereotactic radiosurgery, or SBRT, can be enrolled, but must have completed radiation therapy at least 7 days before starting treatment.
Key exclusion criteria (11 listed)
- Patients who require a VP shunt due to increased intracranial pressure.
- Patients must not have active autoimmune diseases requiring systemic treatment in the past two years (i.e., using disease-modifying agents, corticosteroids, or immunosuppressive drugs). Alternative therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered forms of systemic treatment.
- Subjects who need systemic treatment within 14 days prior to administration of the study drug, including the use of corticosteroids (>4 mg daily dexamethasone equivalent dose) or other immunosuppressive drugs. Inhaled or topical steroids and adrenal replacement therapy at a daily replacement dose >10 mg prednisone equivalent are allowed in the absence of active autoimmune diseases.
- Patients who have previously received PD-1 and/or anti-CTLA-4 therapy are eligible, unless they are experiencing > grade 2 side effects from such treatments. Ongoing physiological replacement doses for adrenal and thyroid insufficiency are allowed in the protocol.
- Patients currently receiving experimental anti-cancer drugs (co-treatment with approved targeted therapies is permitted).
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 |
|---|---|---|
| Intraventricular PemetrexedIntraventricular injection of 30 mg pemetrexed via Ommaya reservoir, once every 4 weeks until disease progression. | Drug | Intraventricular Pemetrexed combined with Nivolumab |
| Intraventricular NivolumabIntraventricular injection of 40 mg nivolumab via Ommaya reservoir, once every 4 weeks until disease progression. | Drug | Intraventricular Pemetrexed combined with Nivolumab |
| Intraventricular DexamethasoneIntraventricular injection of 5mg/2ml pemetrexed via Ommaya reservoir before injection of pemetrexed and nivolumab. | Drug | Intraventricular Pemetrexed combined with Nivolumab |
Primary outcome
Adverse Event
Time frame: 30 days
Per CTCAE version 4.0
1 secondary outcome
objective response rate (ORR)
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Jiayan Chen, M.D. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intraventricular Pemetrexed, Intraventricular Nivolumab and Intraventricular Dexamethasone in people with Leptomeningeal Metastasis, run by Shanghai Cancer Hospital, China 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 18 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 30 Mar 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Min Fan, M.D. (8618121299483, fanming@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2025.