AzTrials
AzTrials

Non-small Cell Lung CancerPhase 2NCT05810350

Aumolertinib Combined Intrathecal Chemotherapy for Leptomeningeal Metastasis From EGFR-Mutated NSCLC and Prognostic Value of Dynamic Changes in cfDNA Profiles

A Phase 2 study testing Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed in people with Non-small Cell Lung Cancer, run by Three Gorges Hospital of Chongqing 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
Search all trials

Trial summary

This is a prospective, open-label, single-arm clinical trial. The aim of this study is to evaluate the efficacy and safety of almonertinib and intrathecal chemotherapy in patients with advanced EGFR mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) and leptomeningeal metastasis, and to explore the… 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?
Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteChina
Study dates
1 Jan 2023to 31 Aug 2025
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

  • Age at least 18 years old.
  • The Eastern Cancer Organization Collaboration Group (ECOG) had a physical fitness score of 0 to 3, and had not worsened in the previous 2 weeks, with a minimum expected survival of 12 weeks.
  • NSCLC confirmed by histology or cytology, positive cerebrospinal fluid cytology, and combined with central nervous system function and brain imaging findings, diagnosed as NSCLC with meningeal metastasis (including advanced patients who had relapsed or were initially diagnosed after previous surgical treatment; GPA is recommended for grading and typing in the diagnosis of meningeal metastasis from lung cancer).
  • Tumor tissue samples or blood samples were tested and confirmed as EGFR sensitive mutations (including exon 19 deletion or L858R, both alone or coexisting with other EGFR site mutations). The first choice is to submit tumor tissue for examination; If the tumor tissue is inaccessible or the subject is not eligible for tissue biopsy, a blood sample may be sent for examination.
  • The patient has implanted an Ommaya capsule;
  • CT examination of clinical symptom areas (spine and/or brain) and/or head within the past 3 months to rule out contraindications to cerebrospinal fluid examination;
Show all 13Show fewer
  • The subjects agreed to provide two cerebrospinal fluid samples (before treatment and within one week after disease progression) for genetic testing;
  • Women of childbearing age need to take appropriate contraceptive measures and should not breastfeed three months after screening and discontinuing study treatment. "Before starting administration, the pregnancy test was negative, or one of the following criteria was met to demonstrate that there was no risk of pregnancy:
  • Postmenopause is defined as amenorrhea at least 12 months after age greater than 50 years and cessation of all exogenous hormone replacement therapy.
  • Women younger than 50 years of age may also be considered postmenopausal if they have amenorrhea for 12 months or more after stopping all exogenous hormone therapy, and their luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels are within the laboratory postmenopausal reference values.
  • Have undergone irreversible sterilization surgery, including hysterectomy, bilateral ovariectomy, or bilateral salpingectomy, except for bilateral tubal ligation.
  • Male subjects should use barrier contraception (i.e., condoms) three months after screening and discontinuation of study treatment.
  • The subject voluntarily participated and signed an informed consent form in writing.

Who cannot join

  • Have received any of the following treatments:
  • Within 4 weeks before the first administration of the investigational drug, the subject had undergone major surgery (such as craniotomy, thoracotomy, or laparotomy). The definition of major surgical surgery refers to Level 3 and Level 4 surgery specified in the "Management Measures for Clinical Application of Medical Technology" implemented on November 1, 2018;
  • Within 7 days before the first administration of the study drug, a strong CYP3A4 inhibitor, inducer, or CYP substrate (CYP2C8, CYP2D6, etc.) was used.
  • Subjects with other malignant tumors, excluding basal cell carcinoma of the skin and carcinoma in situ.
  • At the beginning of the study treatment, there was a residual toxicity greater than CTCAE level 3 that could not be alleviated from previous treatment.
  • There are pleural effusion/peritoneal effusion requiring clinical intervention (patients who do not require drainage of the effusion or who have been stable for 2 weeks or more after drainage can be enrolled); Presence of pericardial effusion (small amounts of pericardial effusion that are stable for 2 weeks or more are allowed to be included in the group). If local use (such as thoracic perfusion) of anti-tumor drugs is used during drainage, and at least 5 drug half-lives or 21 days (whichever is shorter) must be eluted before the first administration of the study treatment before enrollment;
Show all 36Show fewer
  • Subjects are unwilling to provide cerebrospinal fluid samples or clinical information;
  • Subjects have contraindications for cerebrospinal fluid examination;
  • Previously or currently suffering from primary malignant tumors of the central nervous system;
  • Suffering from autoimmune or inflammatory diseases of the central nervous system (not limited to multiple sclerosis, neurosarcoidosis, chronic fungal, rickettsial, or bacterial meningitis);
  • Subjects who are allergic to the MRI contrast agent gadolinium or who cannot tolerate MRI examination (such as having a cardiac pacemaker, having metal in their body, etc.).
  • According to the judgment of the researcher, there are any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active hemorrhagic constitution, or active infection. There is no need to screen for chronic diseases.
  • Clinically severe gastrointestinal dysfunction may affect the intake, transportation, or absorption of drugs, such as inability to take orally, uncontrollable nausea or vomiting, a history of extensive gastrointestinal resection, untreated recurrent diarrhea, atrophic gastritis, untreated stomach diseases requiring long-term administration of mass pump inhibitors, Crohn's disease, ulcerative colitis, and so on.
  • Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis.
  • Meet any of the following cardiac examination results:
  • The mean value of the QT interval (QTcF) corrected by Fridericia's formula from three electrocardiogram (ECG) examinations at rest is>470 msec;
  • resting ECG indicates conduction or ECG morphological abnormalities (such as complete left bundle branch block, 3rd degree atrioventricular block, 2nd degree atrioventricular block, and PR interval>250 msec);
  • The presence of any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome, or any concomitant medication that causes unexplained sudden death or prolongs the QT interval in immediate family members under the age of 40;
  • Left ventricular ejection fraction (LVEF)<50%.
  • Insufficient bone marrow reserve or organ function, reaching any of the following laboratory limits (no corrective treatment within 1 week before laboratory examination and blood sampling):
  • Absolute neutrophil count<1.5 × 109 / L；
  • Platelet count<100 × 109 / L；
  • Hemoglobin<90 g/L (<9 g/dL);
  • If there is no clear liver metastasis, alanine aminotransferase is>3 times the upper normal limit (ULN); If there is liver metastasis, alanine aminotransferase>5 × ULN；
  • If there is no clear liver metastasis, aspartate aminotransferase>3 × ULN； If there is liver metastasis, aspartate aminotransferase>5 × ULN；
  • If there is no clear liver metastasis, total bilirubin>1.5 × ULN； Or presence of Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastasis with total bilirubin>3 × ULN；
  • Creatinine>1.5 × ULN and creatinine clearance<50 mL/min (calculated using the Cockcroft Gault formula); Only when creatinine>1.5 × It is only necessary to confirm the creatinine clearance rate at ULN;
  • Serum albumin (ALB)<28 g/L.
  • Active fungal, bacterial, and/or viral infections that require systemic treatment.
  • Female subjects who are pregnant, nursing, or planning to become pregnant during the study period.
  • Have a history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of radiation pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
  • A history of hypersensitivity to any active or inactive component of aumolertinib, or to drugs with a chemical structure similar to or in the same category as aumolertinib.
  • Patients who are allergic to or contraindicated to pemetrexed.
  • Any serious or uncontrolled ocular lesions (especially severe dry eye syndrome, dry corneal conjunctivitis, severe exposure keratitis, or other diseases that may increase epithelial damage) that, in the judgment of a doctor, may increase the safety risk of the subject; Or eye abnormalities that require surgery or are expected to require surgical treatment during the study period.
  • Subjects who, according to the judgment of the investigator, may have poor compliance with the research procedures and requirements, such as having a clear history of neurological or mental disorders (including epilepsy or dementia), or currently suffering from mental disorders.
  • The investigator determines that there are any conditions that endanger the safety of the subject or interfere with the evaluation of the study, or other conditions that the researcher believes are not suitable for enrollment.

Trial locations and contacts

1 site in 1 country.

China1 site

  • chongqing University Three Gorges Hospital

    Chongqing

Other trials in China

About this study

Official title: The Efficacy and Safety of Aumolertinib Combined Ommaya Reservoir Intrathecal Chemotherapy With Pemetrexed for Leptomeningeal Metastasis From EGFR-mutated NSCLC and Investigate the Efficacy Prognostic Value of Dynamic Changes of cfDNA

This is a prospective, open-label, single-arm clinical trial. The aim of this study is to evaluate the efficacy and safety of almonertinib and intrathecal chemotherapy in patients with advanced EGFR mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) and leptomeningeal metastasis, and to explore the predictive value of dynamic changes of cfDNA in cerebrospinal fluid for efficacy and prognosis. A total of 40 subjects who met the inclusion criteria were enrolled in the study and received almonertinib (165mg, oral, once a day) combined with intrathecal infusion. Before and after treatment, cerebrospinal fluid was extracted for cfDNA detection by a 49 gene detection panel. Treatment continued until disease progression or other discontinuation criteria were met. In addition, the subjects received regular hematological and imaging examinations to evaluate the condition. Finally, through data analysis, the progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), duration of response (DoR), and overall survival (OS) of patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastasis who received almonertinib combined with intrathecal infusion chemotherapy were evaluated. The dynamic changes of cfDNA in cerebrospinal fluid before and after treatment were explored and the correlation between the dynamic changes of cfDNA in cerebrospinal fluid and the therapeutic effect was explored.

Read the detailed description

This study is a prospective, open-label, single-arm clinical trial to explore the efficacy and safety of almonertinib and intrathecal chemotherapy in patients with advanced NSCLC and leptomeningeal metastasis and the predictive value of cfDNA changes for efficacy and prognosis. A total of 40 patients aged 18 years or older with confirmed advanced NSCLC with leptomeningeal metastases and an EGFR sensitive mutation (exon 19 deletion or 21 L858R) are expected to be enrolled. The intervention was almonertinib (165mg orally, once daily) combined with intrathecal infusion therapy (pemetrexed 30 mg by injection on days 1 and 8 of each cycle). Treatment continued until disease progression or other discontinuation criteria were met.

Relevant examinations and data collection during the study were as follows. CSF collection: Approximately 15mL of CSF was collected from each sample, and sampling was performed before C1D1 administration and within one week after PD (24 hours after the previous day's administration). Venous blood sample collection: subjects who underwent CSF sampling were performed before C1D1 and C2D1 administration (24 hours after the previous day's dose) and within 1 week after PD. Before treatment, all enrolled patients underwent neurological examination, complete blood count, serum biochemistry, coagulation indexes, blood tumor markers, cytological and CSF tumor markers, electrocardiogram, brain and spinal cord MRI, chest and abdominal CT, and bone scan. The blood and CSF tests described above were performed for each treatment cycle. Imaging was performed every 2 months or if clinical progression was suspected until death. Before each intrathecal infusion, LM-related neurological symptoms, PS score, Neuro-oncology Working Group (RANO) score, and headache score were assessed and recorded in detail. Adverse events (AEs) were graded and recorded according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

The primary objective was to evaluate the progression-free survival (PFS) of almonertinib versus intrathecal chemotherapy in patients with advanced EGFR mutation-positive NSCLC and leptomeningeal metastases. The secondary study objectives were: first, to evaluate the efficacy of almonertinib and intrathecal chemotherapy in the treatment of advanced NSCLC with leptomeningeal metastases: disease control rate (DCR), objective response rate (ORR), duration of response (DoR), and overall survival (OS); Intracranial: intracranial progression-free survival (iPFS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and intracranial duration of response (iDoR). Second, evaluate the time to symptom improvement of almonertinib versus intrathecal chemotherapy in patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastases. Third, we evaluated the safety of almonertinib and intrathecal infusion chemotherapy in patients with EGFR mutation-positive advanced NSCLC and leptomeningeal metastases. The objectives of this pilot study were as follows: 1) To evaluate the correlation between baseline and post-treatment cfDNA changes in CSF and treatment response; Second, the correlation between baseline CSF cfDNA status and patient prognosis; Third, sensitivity analysis based on baseline CSF cfDNA mutations and leptomeningeal metastases after targeted therapy.

Being tested
Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed
Keywords
EGFR, cfDNA, leptomeningeal metastasis, NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Meningeal Carcinomatosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexedDrug

    Patients receive Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed (30 mg was administered on days 1 and 8) once every 3 weeks.

Study groups in NCT05810350
Study groupRoleWhat they receive
aumolertinib combined Ommaya reservoir intrathecal chemotherapyExperimentalAumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed (30 mg was administered on days 1 and 8) once every 3 weeks.
Receives: Drug: Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed

What is being measured

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

  1. Progression-free survival

    PFS is defined as the time from date of enrollment until the date of disease progression as assessed according to RECIST 1.1 or death from any cause on study.

    Measured: 18 months.

Secondary outcomes (5)

  1. intracranial progress free survival

    iPFS is defined as the time from date of enrollment until the date of disease progression in intrathecal lesions as assessed according to Response Assessment in Neuro-Oncology or death from any cause on study.

    Measured: 18 months.

  2. objective response rate

    ORR is defined as the number of patients with at least 1 visit response of CR (Complete response) or PR (Partial response) according to RECIST 1.1.

    Measured: 18 months.

  3. Disease control rate

    Disease control rate (DCR) is defined as the percentage of participants with disease control best overall response (complete response, partial response or stable disease).

    Measured: 18 months.

  4. overall survival

    OS is defined as time from date of enrollment until date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

    Measured: From baseline until death due to any cause,up to a maximum of approximately 3 years.

  5. Incidence of Adverse Events (AEs)

    AEs are graded according to CTCAE v5.0 and recorded in the case report form.

    Measured: From the screening period to 28 days after treatment completion, approximately 3 years.

Timeline

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

  1. First posted12 Apr 2023
  2. Study start1 Jan 2023
  3. Primary completion31 Aug 2025
  4. Study completion31 Aug 2025

Resources

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
Model description
Aumolertinib
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05810350
Sponsor's protocol ID
2022(No.166)
Status last verified
Sep 2026
First submitted
30 Mar 2023
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed in people with Non-small Cell Lung Cancer, run by Three Gorges Hospital of Chongqing 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 13 inclusion and 36 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 5 Oct 2026. 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?

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?

Progression-free survival (time frame: 18 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 NCT05810350.

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 5 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in