NSCLCPhase 2NCT06339242
A Study of Furmonertinib Combined With Chemotherapy in the Treatment of NSCLC With Leptomeningeal Metastasis
A Phase 2 study testing Furmonertinib in people with NSCLC, run by Jiangsu Province Nanjing Brain Hospital at 1 site in China.
Trial summary
Leptomeningeal metastasis is a fatal complication of advanced lung cancer. There is no standard treatment for leptomeningeal metastasis after third-generation EGFR-TKIs. The Furmonertinib prototype persists longer in brain tissue, and its metabolites can also penetrate the blood-brain barrier. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NSCLC
- What is being tested?
- Furmonertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2024to 31 Jan 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged 18-75 years old (including 18 and 75 years old);
- ECOG PS 0-3 with no deterioration in the first 2 weeks；
- The lowest expected survival time was ≥12 weeks；
- NSCLC patients with EGFR sensitive mutations confirmed by tissue and/or cytology;
- Patients with EGFR sensitive mutations (EGFR exon 19 deletion or EGFR exon 21 L858R mutation) without other driver genes with targeted therapy (such as C797X mutation, MET abnormality, etc.) were enrolled；
- Leptomeningeal metastasis after resistance to third-generation EGFR-TKIs;
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- Histologically confirmed NSCLC LM patients by positive CSF cytology. The diagnosis of LM can be based on MRI with malignant cells in the cerebrospinal fluid, focal or diffuse enhancement of the leptomeninges, and enhancement of nerve roots or ependymal surfaces;
- no severe liver and kidney dysfunction;
- no other serious chronic diseases;
- Women should use adequate contraceptive methods throughout the study; Termination of pregnancy was recommended if pregnancy occurred during the study. Failure to heed the advice was at your own risk.
- Informed consent was signed.
Who cannot join
- Other patients except lung cancer were considered as malignant tumors;
- any unresolved pretreatment toxicity (except alopecia and grade 2 platinum-based neuropathy) greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the initiation of study treatment;
- Refractory nausea, vomiting, or chronic gastrointestinal disease, inability to swallow the study drug, or previous significant intestinal resection surgery, resulting in inadequate absorption of vormetinib;
- Patients with clinical manifestations of nervous system failure included severe encephalopathy, grade Ⅲ-Ⅳ white matter lesions confirmed by imaging examination, moderate or severe coma, and Glasgow coma scale less than 9;
- known history of hypersensitivity reactions to active or inactive excipients of vormetinib or drugs with a similar chemical structure or class to vormetinib;
- any of the following: pregnant women; Women who are lactating; Reluctance among men or women of childbearing potential to use appropriate contraception;
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- previous history of myocardial infarction or other arterial thrombotic diseases (angina pectoris), symptomatic congestive heart failure (New York Heart Association grade ≥2), unstable angina pectoris or arrhythmia; Note: only allowed if the patient had no evidence of active disease for at least 6 months before randomization;
- History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) ≤6 months before enrollment;
- history of hemorrhagic diathesis or coagulopathy;
- lack of adequate bone marrow reserve or organ function (enrollment at investigator's discretion) : absolute neutrophil count <1.0×109/L; Platelet count <75×109/L; Hemoglobin <90 g/L; Alanine aminotransferase > 2.5 times ULN; Aspartate aminotransferase >2.5 times ULN; Total bilirubin > 1.5 times ULN; Or liver metastasis patients AST and/or ALT > 5× ULN, total bilirubin >3×ULN; Serum creatinine >1.5 times ULN and creatinine clearance <50 mL/ minute (measured or calculated by the common formula of Cockcroft and Gault) International normalized ratio (INR)> 1.5 and partial activated prothrombin time (APTT)>1.5×ULN;
- major surgery within 28 days before the administration of the first dose of study drug (in China, major surgery was defined according to the "Administrative Measures for the Clinical Application of Medical Technology" which was implemented on May 1, 2009 and referred to grade 3 and 4 surgery);
- evidence of any severe or uncontrolled systemic illness, including uncontrolled hypertension, diabetes mellitus, and active bleeding, any nonadherence to the study or any active infection, including uncontrolled hepatitis B, hepatitis C, and human immunodeficiency virus (HIV), as considered by the investigator to be detrimental to patient participation or adherence to the protocol;
- For women of childbearing age, a negative urine or serum pregnancy test should be performed 3 days prior to receiving the first dose of study drug; Participants and their sexual partners were required to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment period. If a subject or a subject's partner becomes pregnant during the study, inform your study doctor immediately and the study doctor advises you or your partner to terminate the pregnancy; If you persist with the pregnancy, your doctor, with your consent, will continue to monitor the mother and baby until birth.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Nanjing Brain Hospital
Nanjing, Jiangsu, 210029
fang S Cun, 83728558 ext. 025, fang1984@aliyun.com
About this study
Official title: A Single-arm, Prospective Clinical Study of Double Dose of Furmonertinib Combined With Lateral Ventricular Chemotherapy in the Treatment of EGFR-mutant Lung Cancer With Leptomeningeal Metastasis After Third-generation EGFR-TKIs Resistance
Leptomeningeal metastasis is a fatal complication of advanced lung cancer. There is no standard treatment for leptomeningeal metastasis after third-generation EGFR-TKIs. The Furmonertinib prototype persists longer in brain tissue, and its metabolites can also penetrate the blood-brain barrier. Ommaya cystlateral ventricle chemotherapy can quickly control the progression of intracranial lesions. The aim of this study is to evaluate the LM progression-free survival (LM-PFS) of Furmonertinib combined with lateral ventricular chemotherapy in the treatment of leptomeningeal metastatic NSCLC after third-generation EGFR-TKIs resistance.
Read the detailed description
At present, there is still a lack of prospective, randomized clinical trials on the treatment of LM, most of which are small sample studies, retrospective analysis and clinical experience, with low level of evidence and limited clinical guidance. Improving the clinical outcome of patients with LM has become an urgent problem to be solved in clinical treatment. Our previous team has reported for the first time that Furmonertinib combined with lateral ventricular chemotherapy can not only effectively improve the neurological symptoms caused by LM, but also prolong the survival time of patients with limited and controllable side effects, which provides a new treatment approach for EGFR mutation-positive NSCLC accompanied by LM. Therefore, based on the structural and pharmacological differences between the three generations of EGFR-TKIs, combined with Ommaya lateral ventricle chemotherapy can rapidly control the progression of intracranial lesions, The aim of this study is to explore whether double dose of Furmonertinib combined with Ommya intracapsular ventricle chemotherapy can provide survival benefits for advanced EGFR mutation-positive NSCLC with leptomeningeal metastasis after third-generation EGFR-Tkis.
- Conditions
- NSCLC
- Being tested
- Furmonertinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurmonertinibDrug
Also called Furmonertinib Mesylate
After completion of all screening activities, eligible patients were confirmed to enter the study. All patients will receive study treatment, Furmonertinib tablets 160mg, oral, once daily, lateral ventricular chemotherapy with Ommaya capsule technique until disease progression, intolerable toxicity, death, withdrawal of informed consent.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Patients who met the inclusion criteria were given Furmonertinib tablets 160mg daily for continuous oral administration, and combined with Ommaya capsule technology lateral ventricle chemotherapy for local treatment until the disease progression of meningeal metastases or intolerance or death. Receives: Drug: Furmonertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
LM-PFS（progression-free survival）
assessments, based on neuroimaging RANO-LM
Measured: Up to 2 years
LM-ORR（Objective response rate）
assessments, based on neuroimaging RANO-LM
Measured: Up to 2 years
Secondary outcomes (3)
LM-OS
defined as time from LM diagnosis to death due to any cause or last follow-up
Measured: Up to 2 years
Incidence of Treatment-Emergent Adverse Events
Occurrence and severity of AEs by NCI CTCAE v5.0
Measured: Up to 2 years
PFS
Proportion of patients progression-free by investigator assessment per RECIST v1.1
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2024
- Study start1 Jan 2024
- Primary completion1 Jul 2025 (estimated)
- Study completion31 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies 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
- Jiangsu Province Nanjing Brain Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- fang S Cun, M.D., Study chair, Nanjing Brain Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06339242
- Sponsor's protocol ID
- 2024-01-NSCLC
- Status last verified
- Mar 2024
- First submitted
- 25 Mar 2024
- Last updated
- 1 Apr 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 1 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Prospective Clinical Study of Double Dose of Furmonertinib Combined With Lateral Ventricular Chemotherapy in the Treatment of EGFR-mutant Lung Cancer With Leptomeningeal Metastasis After Third-generation EGFR-TKIs Resistance
- ClinicalTrials.gov ID
- NCT06339242
- Acronym / sponsor ID
- 2024-01-NSCLC
- Conditions
- NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Jiangsu Province Nanjing Brain HospitalUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 1 Apr 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.
Leptomeningeal metastasis is a fatal complication of advanced lung cancer. There is no standard treatment for leptomeningeal metastasis after third-generation EGFR-TKIs. The Furmonertinib prototype persists longer in brain tissue, and its metabolites can also penetrate the blood-brain barrier. Ommaya cystlateral ventricle chemotherapy can quickly control the progression of intracranial lesions. The aim of this study is to evaluate the LM progression-free survival (LM-PFS) of Furmonertinib combined with lateral ventricular chemotherapy in the treatment of leptomeningeal metastatic NSCLC after third-generation EGFR-TKIs resistance.
Detailed description
At present, there is still a lack of prospective, randomized clinical trials on the treatment of LM, most of which are small sample studies, retrospective analysis and clinical experience, with low level of evidence and limited clinical guidance. Improving the clinical outcome of patients with LM has become an urgent problem to be solved in clinical treatment. Our previous team has reported for the first time that Furmonertinib combined with lateral ventricular chemotherapy can not only effectively improve the neurological symptoms caused by LM, but also prolong the survival time of patients with limited and controllable side effects, which provides a new treatment approach for EGFR mutation-positive NSCLC accompanied by LM. Therefore, based on the structural and pharmacological differences between the three generations of EGFR-TKIs, combined with Ommaya lateral ventricle chemotherapy can rapidly control the progression of intracranial lesions, The aim of this study is to explore whether double dose of Furmonertinib combined with Ommya intracapsular ventricle chemotherapy can provide survival benefits for advanced EGFR mutation-positive NSCLC with leptomeningeal metastasis after third-generation EGFR-Tkis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: FurmonertinibPatients who met the inclusion criteria were given Furmonertinib tablets 160mg daily for continuous oral administration, and combined with Ommaya capsule technology lateral ventricle chemotherapy for local treatment until the disease progression of meningeal metastases or intolerance or death. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- aged 18-75 years old (including 18 and 75 years old);
- ECOG PS 0-3 with no deterioration in the first 2 weeks；
- The lowest expected survival time was ≥12 weeks；
- NSCLC patients with EGFR sensitive mutations confirmed by tissue and/or cytology;
- Patients with EGFR sensitive mutations (EGFR exon 19 deletion or EGFR exon 21 L858R mutation) without other driver genes with targeted therapy (such as C797X mutation, MET abnormality, etc.) were enrolled；
Key exclusion criteria (13 listed)
- Other patients except lung cancer were considered as malignant tumors;
- any unresolved pretreatment toxicity (except alopecia and grade 2 platinum-based neuropathy) greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the initiation of study treatment;
- Refractory nausea, vomiting, or chronic gastrointestinal disease, inability to swallow the study drug, or previous significant intestinal resection surgery, resulting in inadequate absorption of vormetinib;
- Patients with clinical manifestations of nervous system failure included severe encephalopathy, grade Ⅲ-Ⅳ white matter lesions confirmed by imaging examination, moderate or severe coma, and Glasgow coma scale less than 9;
- known history of hypersensitivity reactions to active or inactive excipients of vormetinib or drugs with a similar chemical structure or class to vormetinib;
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 |
|---|---|---|
| FurmonertinibAlso: Furmonertinib MesylateAfter completion of all screening activities, eligible patients were confirmed to enter the study. All patients will receive study treatment, Furmonertinib tablets 160mg, oral, once daily, lateral ventricular chemotherapy with Ommaya capsule technique until disease progression, intolerable toxicity, death, withdrawal of informed consent. | Drug | Experimental group |
Primary outcome
LM-PFS（progression-free survival）
Time frame: Up to 2 years
assessments, based on neuroimaging RANO-LM
LM-ORR（Objective response rate）
Time frame: Up to 2 years
assessments, based on neuroimaging RANO-LM
3 secondary outcomes
LM-OS
Time frame: Up to 2 years
Incidence of Treatment-Emergent Adverse Events
Time frame: Up to 2 years
PFS
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2024.
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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.
fang S Cun, M.D. study chair
Nanjing Brain Hospital
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 Furmonertinib in people with NSCLC, run by Jiangsu Province Nanjing Brain 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 11 inclusion and 13 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 1 Apr 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 fang S Cun (83728558, fang1984@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LM-PFS（progression-free survival） (time frame: Up to 2 years). 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?
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 1 Apr 2024.