Non-small Cell Lung CancerPhase 2NCT06537297
Intrathecal Pemetrexed Combined With High-dose Furmonertinib and Beva for EGFR-m NSCLC With Leptomeningeal Metastases
A Phase 2 study testing Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab in people with Non-small Cell Lung Cancer, run by Hunan Province Tumor Hospital at 1 site in China.
Trial summary
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant non-small cell lung cancer patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2024to 30 Apr 2026
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
- 2. Age ≥ 18 years.
- 3. Histopathology confirmed Non-small cell lung cancer.
- 4. confirmed or probable leptomeningeal metastases according to EANO-ESMO guidelines or known leptomeningeal metastases progression after third generation of EGFR-TKIs failure.
- 5.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
- 6.ECOG 0 - 2.
- 7. Predicted survival ≥ 12 weeks.
- 8. Adequate bone marrow hematopoiesis and organ function.
Who cannot join
- 1. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
- 2. Subjects who have received any of the following treatments must be excluded: Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
- 3. Presence of spinal cord compression.
- 4. History of other malignant tumors within 2 years.
- 5. Adverse events (except alopecia of any degree) of CTCAE > grade 4 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
- 6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
Show all 15Show fewer
- 7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
- 8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
- 9. Heart-related diseases or abnormalities
- 10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
- 11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb Furmonertinib due to previous bowel resection.
- 12. Live vaccine was given 2 weeks before the first medication.
- 13. Women who are breastfeeding or pregnant.
- 14. Hypersensitivity to the test drug and the ingredients.
- 15. Other conditions assessed by the investigator to be unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country.
Liang zeng, MD contact
China1 site
Hunan Cancer Hospital
Changsha, Hunan, 410013
Yongchang Zhang, MD, +86 731 89762323, zhangyongchang@csu.edu.cn
About this study
Official title: The Efficacy and Safety of Intrathecal Pemetrexed With High-dose Furmonertinib Plus Bevacizumab for EGFR-mutant NSCLC Patients With Leptomeningeal Metastases Resistant to Third-generation EGFR-TKIs: A Phase II Study.
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant non-small cell lung cancer patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs.
Read the detailed description
This prospective interventional study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs.
Approximately 30 EGFR-mutant Non-small cell lung cancer patients with leptomeningeal metastasis or leptomeningeal progression after resistant to third generation EGFR-TKIs were enrolled and treated with intrathecal pemetrexed with high-dose furmonertinib plus bevacizumab. cerebrospinal fluid and blood samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms. Second-generation gene detection will be performed to identify potential resistance mechanisms to pemetrexed. The study is expected to commence recruitment in mainland China in about August 2024. It is expected that the trial will end in April 2026.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumabDrug
Also called intrathecal pemetrexed, high-dose furmonertinib, bevacizumab
- Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly;
- Furmonertinib(160mg QD);
- bevacizumab(5mg/kg，once monthly) until progressive disease.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal Pemetrexed with double Furmonertinib plus bevacizumab | Experimental | Not described Receives: Drug: Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
LM-overall survival
LM-OS was defined as the duration from the start of intrathecal pemetrexed to patient death
Measured: Time from first subject dose to study completion, or up to last follow up
Secondary outcomes (3)
Extracranial progression-free survival
Extracranial Progression-Free survival was defined as the duration from the start of intrathecal pemetrexed to the progression of extracranial disease or patient death or last follow up
Measured: Time from first dose to the progression of extracranial disease or patient death or last follow up
Clinical response rate
Clinical Response Rate was defined as the ratio of the patient whose neurological symptoms and KPS improved according to the criteria of clinical response
Measured: Time from first dose to the improvement of neurological symptoms and KPS score
Adverse events (AEs)
Number of participants with adverse events (AEs) according to CTCAE 5.0
Measured: From first dose until 28 days after the last dose, up to 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2024
- Study start30 Sep 2024 (estimated)
- Primary completion31 Aug 2025 (estimated)
- Study completion30 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Province Tumor Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongchang Zhang, Hunan Province Tumor Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06537297
- Sponsor's protocol ID
- 20240801
- Status last verified
- Sep 2024
- First submitted
- 31 Jul 2024
- Last updated
- 20 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Intrathecal Pemetrexed With High-dose Furmonertinib Plus Bevacizumab for EGFR-mutant NSCLC Patients With Leptomeningeal Metastases Resistant to Third-generation EGFR-TKIs: A Phase II Study.
- ClinicalTrials.gov ID
- NCT06537297
- Acronym / sponsor ID
- 20240801
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hunan Province Tumor HospitalUniversity, hospital or other
- Study start
- 30 Sep 2024 (estimated)
- Primary completion
- 31 Aug 2025 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 5 Aug 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.
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant non-small cell lung cancer patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs.
Detailed description
This prospective interventional study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs.
Approximately 30 EGFR-mutant Non-small cell lung cancer patients with leptomeningeal metastasis or leptomeningeal progression after resistant to third generation EGFR-TKIs were enrolled and treated with intrathecal pemetrexed with high-dose furmonertinib plus bevacizumab. cerebrospinal fluid and blood samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms. Second-generation gene detection will be performed to identify potential resistance mechanisms to pemetrexed. The study is expected to commence recruitment in mainland China in about August 2024. It is expected that the trial will end in April 2026.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal Pemetrexed with double Furmonertinib plus bevacizumab | Experimental | Drug: Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
- 2. Age ≥ 18 years.
- 3. Histopathology confirmed Non-small cell lung cancer.
- 4. confirmed or probable leptomeningeal metastases according to EANO-ESMO guidelines or known leptomeningeal metastases progression after third generation of EGFR-TKIs failure.
- 5.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
Key exclusion criteria (15 listed)
- 1. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
- 2. Subjects who have received any of the following treatments must be excluded: Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
- 3. Presence of spinal cord compression.
- 4. History of other malignant tumors within 2 years.
- 5. Adverse events (except alopecia of any degree) of CTCAE > grade 4 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
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 |
|---|---|---|
| Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumabAlso: intrathecal pemetrexed, high-dose furmonertinib, bevacizumab* Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly; * Furmonertinib(160mg QD); * bevacizumab(5mg/kg，once monthly) until progressive disease. | Drug | Intrathecal Pemetrexed with double Furmonertinib plus bevacizumab |
Primary outcome
LM-overall survival
Time frame: Time from first subject dose to study completion, or up to last follow up
LM-OS was defined as the duration from the start of intrathecal pemetrexed to patient death
3 secondary outcomes
Extracranial progression-free survival
Time frame: Time from first dose to the progression of extracranial disease or patient death or last follow up
Clinical response rate
Time frame: Time from first dose to the improvement of neurological symptoms and KPS score
Adverse events (AEs)
Time frame: From first dose until 28 days after the last dose, up to 24 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
Related trials for Non-small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
Liang zeng, MD 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 Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab in people with Non-small Cell Lung Cancer, run by Hunan Province Tumor Hospital 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 8 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 20 Sep 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yongchang Zhang, MD (+8613873123436 ext. 7+861383123436, zhangyongchang@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LM-overall survival (time frame: Time from first subject dose to study completion, or up to last follow up). 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 20 Sep 2024; AzTrials last refreshed its copy on 7 Nov 2026.