Evaluating High-dose Furmonertinib with Bevacizumab and Pemetrexed for EGFRm NSCLC with Leptomeningeal Metastasis

NCT06643000 | Recruiting

• 1 other identifier: TA2024-690
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this clinical study is to evaluate the efficacy of high-dose furmonertinib combined with bevacizumab and pemetrexed (triple therapy) in the treatment of non-small cell lung cancer (NSCLC) with leptomeningeal metastasis and epidermal growth factor receptor mutation (EGFRm) through overall survival (OS). The secondary objectives are to further assess the efficacy of the triple therapy in patients with EGFRm and leptomeningeal metastasis, including time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), and clinical response rate.The study will also evaluate the impact of the triple therapy on quality of life using the EORTC QLQ-C30 scale and assess the safety of the therapy in EGFRm NSCLC patients with leptomeningeal metastasis, focusing primarily on adverse events and their severity (graded according to CTCAE v5.0), as well as their frequency.The exploratory objectives are to assess changes in intracranial pressure and the improvement rate of cerebrospinal fluid (CSF) before and after the triple therapy treatment. Additionally, the study will compare the genomic and epigenomic profile changes in circulating tumor DNA (ctDNA) from peripheral blood and cell-free DNA (cfDNA) from cerebrospinal fluid before and after treatment, and analyze their correlation with clinical outcomes, drug efficacy, and other clinical indicators. The primary endpoint of this study is overall survival (OS). The secondary endpoints include time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), clinical response rate, and quality of life assessment (EORTC QLQ-C30).The safety endpoints are adverse events and their severity (graded according to CTCAE v5.0), as well as the frequency of occurrence. A total of 60 patients are planned to be enrolled, targeting eligible advanced NSCLC patients with EGFR mutations and leptomeningeal metastasis. The intervention consists of furmonertinib (240 mg/d, po) combined with bevacizumab (15 mg/kg, every 3 weeks, ivgtt) and pemetrexed (50 mg) intrathecal chemotherapy / pemetrexed (500 mg/m²) intravenous chemotherapy, administered every 3 weeks.

Conditions

Non-small Cell Lung Cancer; Leptomeningeal Metastasis; EGFR Gene Mutation

Outcome Measures

Primary Outcomes (1)

• OS

  overall survive time

  the time between the date of enrollment and the date of death from any cause

Secondary Outcomes (3)

• TTF

  The time interval from the start of the triple therapy to treatment failure

• ORR-LM

  the proportion of patients whose leptomeningeal lesions achieve a complete response (CR) or partial response (PR) during the study period from the first administration of the study drug until leptomeningeal disease progression

• CRR

  the proportion of patients whose CR, OR, or PR lasts for at least one week

Study Arms (1)

Triple therapy

EXPERIMENTAL

furmonertinib combined with bevacizumab and pemetrexed

Drug: furmonertinib

Interventions

furmonertinib DRUG

furmonertinib (240 mg/d,po) combined with bevacizumab (15 mg/kg, every 3 weeks, ivgtt) and pemetrexed (50 mg) intrathecal chemotherapy / pemetrexed (500 mg/m²) intravenous chemotherapy, administered every 3 weeks.

Also known as: bevacizumab, pemetrexed

Triple therapy

Eligibility Criteria

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

You may qualify if:

• Have obtained written informed consent from the patient or his or her legal representative;
• The patient is ≥18 years old, male or female;
• Non-small cell lung cancer confirmed by histological or cytological pathology;
• Genetic testing confirming positive for classical or non-classical EGFR mutations;
• After comprehensive clinical evaluation according to the "EANO-ESMO" meningeal metastasis diagnostic criteria, the comprehensive clinical evaluation of patients with definite meningeal metastasis included symptom evaluation, imaging evaluation, and/or cerebrospinal fluid pathology evaluation;
• Patients with newly diagnosed leptomeningeal metastases and those with disease progression after previous antineoplastic therapy were eligible;
• ECOG Performance Status 0-3;
• Prior treatment with radiation or surgery targeting the central nervous system is permitted;
• Admit patients with CNS symptoms or signs, but those symptoms or signs are not life threatening;
• Fertile men or women with the possibility of becoming pregnant must use a highly effective method of contraception (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) during the course of the trial and continue contraception for 12 months after the end of treatment.

You may not qualify if:

• )Patients currently have tumors other than NSCLC; 2)Have had or have a history of other malignancies within the last 5 years, other than basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast that have been effectively controlled; 3)Serious digestive tract diseases that affect drug use and absorption, including but not limited to peptic ulcer, inflammatory bowel disease, etc.
• )Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension, diabetes, and active bleeding, any that the investigator deems to be detrimental to the patient's participation in the study or to adherence to the protocol, or active infections including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV); 5)A history of interstitial lung disease, drug-induced interstitial lung disease, prior history of radiation pneumonia requiring steroid treatment, or any evidence of active interstitial lung disease; 6)The presence of significant arrhythmias (such as prolonged QT interval \> 500ms) or heart failure (left ventricular ejection fraction \< 50%) 7)Pregnant or lactating women; 8)Patients who received a live vaccine within 4 weeks before treatment began; 9)Patients who are or have been involved in another clinical study within 4 weeks; 10)Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase the risks associated with participating in the study or may interfere with the interpretation of the study results; Or subjects who may not be able to complete the study or comply with the requirements of the study (for administrative or other reasons).

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (2)

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Interventions

aflutinib; Bevacizumab; 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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Qiming Wang, MD

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qi Zhao, MS

CONTACT

+86 15515521691; 15515521691@163.com

Haiyang Chen, MD

CONTACT

+86 0371 65588251; chenocean017@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of Internal Medicine

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 15, 2024
• Study Start: December 20, 2024
• Primary Completion: March 30, 2025
• Study Completion: May 30, 2025
• Last Updated: March 6, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)