Clinical trial NCT06812871: High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis
Official title: A Single-arm, Multicenter, Phase 2 Study of High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer Metastatic
Keywords: EGFR mutated
meningeal metastasis
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: the study conducted to evaluate the efficacy and safety of high-dose furmonertinib (160 mg qd) combined with bevacizumab and pemetrexed intrathecal chemotherapy in NSCLC patients with EGFR mutations and meningeal metastases.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological localization is NSCLC;
* confirmed EGFR exon 19 deletion mutation(19del) or EGFR exon 21L858R mutation (L858R) or EGFR exon 20 T790M mutation (T790M)）;
* Clinical diagnosis of meningeal aggravation: clinical symptoms of intracranial hypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebral MRI diagnosis of meningeal aggravation) or cerebrospinal fluid cytology confirmation;
* for patients with symptoms who are considered to need temporary brain local. Treatment of cough receiving adrenal corticosteroids must be kept stable or reponse for at least 1 week before the first trial of the drug preparation;
* Newly diagnosed meningeal metastasis, including meningeal metastasis after previous brain surgery and/or local radiotherapy for solid metastatic disease;
* Patients had not received previous systemic treatment for advanced NSCLC or had meningeal metastases after treatment with one third-generation EGFR-TKI.
* Obtain informed consent signed by the patient's legal representative;
* Aged ≥18 years and ≤75 years;
* Eastern Tourism Cooperation Group (ECOG) Physical condition evaluation 0-1;
* Life expectancy ≥12 week;
* Able to follow the requirements of the study protocol and confirmation procedures, and able to accept cranial wall medications;
* contraception.

Exclusion Criteria:

* Mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as the main pathological type;
* Known EGFR exon 20 C797X mutation (C797X);
* history of hypersensitivity reaction to active or inactive excipients of furmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or class to the investigational drug;
* Brain metastases have previously received whole-brain radiotherapy;
* Currently participating in an interventional clinical trial, or having received other study drugs or study devices within 4 weeks before the first study drug;
* Patients who have received solid organ or blood system transplantation;
* Patients with severe intracranial hypertension symptoms that cannot be relieved by discontinuation of dexamethasone and/or glycol treatment, or patients in intensive care;
* Ensure control of the patient's symptomatic pericardial, peritoneal, and pleural effusions;
* History of cancer in the last five years Other malignancies or a history of other malignancies;
* Recent active digestive events, such as duodenitis, ileitis, intestinal perforation, intestinal catheters, or other conditions that may cause gastrointestinal tract or perforation; or refractory vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or previous colorectal cancer resection that prevents adequate drug absorption;
* The patient has a physique that is prone to Japanese language learning or has active Japanese language learning;Central squamous cell carcinoma orPatients at greater risk for hemoptysis; Any diamond event ≥ CTCAE grade 3, presence of open wounds, injuries or fractures in the 28th century before the first creation; if in the first Asthma was accepted 28 days before the organization meeting, the wound treatment should be evaluated by the interval period;
* History of arterial thromboembolism within the last 6 months, including vascular cerebral accident, myocardial infarction, transient cerebral contemplation;
* History of grade 4 venous thrombosis within the last 6 months, including fire embolism;
* The presence of any severe or uncontrolled systemic evidence, including difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), uncontrolled diabetes, etc.;
* Active infections include, for example, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infections (including those requiring intravenous therapy, active hepatitis B infection includes patients with positive hepatitis B surface test based on serological assessment and hepatitis B virus DNA \>1000 copies/ml);
* previous history of interstitial lung disease, drug-induced interstitial lung disease, pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease;
* The first 28-day inspection of the drug preparation showed Lack of adequate bone marrow reserve or organ function（Within 2 weeks before blood test,No blood transfusion or blood products, granulocyte colony-stimulating factor or other hematopoietic stimulating factors were used for repair）:

  * Absolute neutrophil count \<1.5 × 109/L; continuous count \<100×109/L; hemoglobin \<90 g/L;
  * Alanine aminotransferase \> 2.5 times Upper limit of normal value (Upper limit of normal）; Aspartate aminotransferase\>2.5 times ULN; Total bilirubin\>1.5 times ULN;or liver transplant patients with AST and/or ALT \> 5× ULN;
  * Albumin \<30 g/L;
  * Serum creatinine \>1.5 times ULN, and Creatinine clearance \<50 mL/min（Measured or calculated by Cockcroft and Gault formula);
  * International normalized ratio (INR) \> 1.5,Partially activated zymogen time（APTT\>1.5 times Upper limit of normal;
  * Urine protein ≥++, and 24-hour protein \>2.0g;
* Any of the following Bishop criteria:

  * Clinically significant resting electrocardiogram rhythm, respiratory, or morphological abnormalities, such as left bundle branch block, third-degree myocardial insufficiency, and second-degree myocardial insufficiency, within 28 days before the first study drug perfume;
  * Possibility Interphase Factors that increase the risk of prolonged or arrhythmic events, such as heart failure, congenital long Quantum Dots Syndrome, long Quantum Dots Family history or first-degree relatives 40 Sudden death due to coma or known prolonged Quantum Dots Any sudden or difficult to fully compensate low potassium tariffs, low tariff tariffs, and low tariff-to-tariff tariffs during the period;
  * Left ventricular ejection fraction (LVEF)Left ventricular ejection fraction）\<50%, recent History of myocardial infarction, severe or unstable angina, or coronary artery bypass grafting within the past month or heart failure≥New York Heart Association (New York Heart Association (NYHA) 2 class;
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Intracranial progression-free survival
timeFrame: The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first, assessed up to 24 months
Secondary outcomes:
measure: systemic progression-free survival
timeFrame: The time from receipt of study treatment to systemic PD or to death due to any cause,whichever came first, assessed up to 24 months.
measure: intracranial objective response rate
timeFrame: The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment, through study completion, an average of 12 months.
measure: overall survival
timeFrame: The time interval between enrollment and death from any cause,,whichever came first, assessed up to 24 months.
measure: safety and tolerability
timeFrame: adverse events will be reported and graded according to the National Cancer Institute (NCI) CTCAE version 5.0.,assessed up to 24 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
References: