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

NCT05810350 | Unknown Phase 2

• 1 other identifier: 2022(No.166)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Non-small Cell Lung Cancer

Keywords

EGFR; cfDNA; leptomeningeal metastasis; NSCLC

Outcome Measures

Primary Outcomes (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.

  18 months.

Secondary Outcomes (5)

• intracranial progress free survival

  18 months.

• objective response rate

  18 months.

• Disease control rate

  18 months.

• overall survival

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

• Incidence of Adverse Events (AEs)

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

Study Arms (1)

aumolertinib combined Ommaya reservoir intrathecal chemotherapy

EXPERIMENTAL

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

Drug: Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed

Interventions

Aumonertinib 165mg orally once daily and intrathecal chemotherapy with pemetrexed DRUG

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.

aumolertinib combined Ommaya reservoir intrathecal chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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:

Sponsors & Collaborators

• Three Gorges Hospital of Chongqing University: lead

Study Sites (1)

chongqing University Three Gorges Hospital

Chongqing, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Interventions

Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Wei Wang, doctor

CONTACT

13635324483; 19574605@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Aumolertinib

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: April 12, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 13, 2023

Record last verified: 2023-04

Locations

CN (1)