Leptomeningeal MetastasisNCT06304441
Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer
A study testing Osimertinib and Pemetrexed in people with Leptomeningeal Metastasis, run by Guangzhou Medical University at 1 site in China.
Trial summary
Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). 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?
- Osimertinib and Pemetrexed
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 18 Apr 2024to Sep 2026
- Phase
- Interventional
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged between 18 and 75 years.
- Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).
- Confirmed diagnosis of leptomeningeal metastasis according to ESMO/EANO guidelines.
- 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.
- Patients with poor compliance or other reasons that were unsuitable for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Third People's Hospital of Huizhou (Huizhou Hospital of Guangzhou Medical University)
Huizhou, Guangdong
Zhenyu Pan, +8615804302753, dr-zypan@163.com
Guozi Yang, +8615804302755, guoziyang_1982@163.com
About this study
Official title: A Clinical Trial of Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer
Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in the treatment of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. Due to its small molecule properties, it can effectively penetrate the central nervous system barrier and deliver an effective antitumor effect. An international multi-center clinical study published in 2019 confirmed that double-dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R/T790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, whether third-generation small molecule TKI drugs (e.g. 'osimertinib') combined with intrathecal pemetrexed could benefit patients with LM from EGFR- mutant NSCLC remains undetermined.
Read the detailed description
The aim of this Study is to compare the effects of intra-pemetrexed Plus third-generation small molecule TKI drugs (e.g. 'osimertinib') versus third-generation small molecule TKI drugs alone in leptomeningeal metastasis from EGFR mutation positive NSCLC.
- Conditions
- Leptomeningeal Metastasis
- Being tested
- Osimertinib, Pemetrexed
- Keywords
- Leptomeningeal metastasis, Intrathecal chemotherapy, Pemetrexed, Third-generation small molecule TKI drugs, Osimertinib, Epidermal growth factor receptor mutation
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OsimertinibDrug
Double-dose of TKI (e.g. 'osimertinib' 160 mg) was administered orally once daily until disease progression or unmanageable drug-related toxicity.
PemetrexedDrug
Pemetrexed 15 mg was administered with dexamethasone 5 mg via intraventricular or via lumbar puncture. First, induction intrathecal chemotherapy, twice per week for 2 weeks; then consolidation intrathecal chemotherapy, once per week for 4 weeks; and maintenance intrathecal chemotherapy, once per month until disease progression or unmanageable drug-related toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Intra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib') Receives: Drug: Osimertinib; Drug: Pemetrexed |
| Group B | Active comparator | Third-generation small molecule TKI drugs (e.g. 'osimertinib') alone Receives: Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Secondary outcomes (2)
Overall survival
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
Measured: 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).
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 date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start18 Apr 2024
- Primary completion20 Jun 2026 (estimated)
- Study completionSep 2026 (estimated)
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 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhenyu Pan, Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06304441
- Sponsor's protocol ID
- IPVO
- Status last verified
- Sep 2025
- First submitted
- 5 Mar 2024
- Last updated
- 29 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
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 32733606Pan 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 31544065Yang JCH, Kim SW, Kim DW, Lee JS, Cho BC, Ahn JS, Lee DH, Kim TM, Goldman JW, Natale RB, Brown AP, Collins B, Chmielecki J, Vishwanathan K, Mendoza-Naranjo A, Ahn MJ. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020 Feb 20;38(6):538-547. doi: 10.1200/JCO.19.00457. Epub 2019 Dec 6.
PubMed 31809241
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06304441
- Acronym / sponsor ID
- IPVO
- Conditions
- Leptomeningeal Metastasis
- Keywords
- Leptomeningeal metastasis, Intrathecal chemotherapy, Pemetrexed, Third-generation small molecule TKI drugs, Osimertinib, Epidermal growth factor receptor mutation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- 18 Apr 2024 (actual)
- Primary completion
- 20 Jun 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 12 Mar 2024 (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.
Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in the treatment of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. Due to its small molecule properties, it can effectively penetrate the central nervous system barrier and deliver an effective antitumor effect. An international multi-center clinical study published in 2019 confirmed that double-dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R/T790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, whether third-generation small molecule TKI drugs (e.g. 'osimertinib') combined with intrathecal pemetrexed could benefit patients with LM from EGFR- mutant NSCLC remains undetermined.
Detailed description
The aim of this Study is to compare the effects of intra-pemetrexed Plus third-generation small molecule TKI drugs (e.g. 'osimertinib') versus third-generation small molecule TKI drugs alone in leptomeningeal metastasis from EGFR mutation positive NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Osimertinib, Drug: PemetrexedIntra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib') |
| Group B | Active comparator | Drug: OsimertinibThird-generation small molecule TKI drugs (e.g. 'osimertinib') alone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female aged between 18 and 75 years.
- Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).
- Confirmed diagnosis of leptomeningeal metastasis according to ESMO/EANO guidelines.
- Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
- No history of severe nervous system disease.
Key exclusion criteria (3 listed)
- 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.
- Patients with poor compliance or other reasons that were unsuitable for this study.
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 |
|---|---|---|
| OsimertinibDouble-dose of TKI (e.g. 'osimertinib' 160 mg) was administered orally once daily until disease progression or unmanageable drug-related toxicity. | Drug | Group A, Group B |
| PemetrexedPemetrexed 15 mg was administered with dexamethasone 5 mg via intraventricular or via lumbar puncture. First, induction intrathecal chemotherapy, twice per week for 2 weeks; then consolidation intrathecal chemotherapy, once per week for 4 weeks; and maintenance intrathecal chemotherapy, once per month until disease progression or unmanageable drug-related toxicity. | Drug | Group A |
Primary outcome
Clinical response rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
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.
2 secondary outcomes
Overall survival
Time frame: 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).
Incidence of treatment-related adverse events
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
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 29 Sep 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.
- Background: PubMed 31809241Yang JCH, Kim SW, Kim DW, Lee JS, Cho BC, Ahn JS, Lee DH, Kim TM, Goldman JW, Natale RB, Brown AP, Collins B, Chmielecki J, Vishwanathan K, Mendoza-Naranjo A, Ahn MJ. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020 Feb 20;38(6):538-547. doi: 10.1200/JCO.19.00457. Epub 2019 Dec 6.
- Individual participant dataSharing planned: Yes
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Osimertinib and Pemetrexed in people with Leptomeningeal Metastasis, run by Guangzhou Medical 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 6 inclusion and 3 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 29 Sep 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.
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 Zhenyu Pan (+8615804302753, dr-zypan@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response rate (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.). 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 NCT06304441, 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 29 Sep 2025.