Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in Patients With LM Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI

Trial Title: Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in Patients With LM Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI

NCT ID: NCT06441045

Condition: Leptomeningeal Metastasis

Conditions: Official terms:
Neoplasm Metastasis
Pemetrexed

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Double Dose of Third-generation EGFR-TKI
Description: Double Dose of Third-generation EGFR-TKI
Arm group label: Double Dose of Third-generation EGFR-TKI
Arm group label: Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed

Intervention type: Drug
Intervention name: Intrathecal Pemetrexed
Description: Intrathecal Pemetrexed
Arm group label: Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed

Summary: We aim to compare the efficacy and safety of double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus double Dose of Third-generation EGFR-TKI in patients with leptomeningeal progression following the treatment of routine dose of EGFR-TKI,

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age 18 years at the time of signing informed consent, both sexes; - advanced or metastatic NSCLC, TNM stage IV according to the eighth edition of IASLC 2015; - with EGFR sensitive mutation (exon 19 deletion or L858R mutation), LM progression after conventional doses of three generation EGFR targeted agents (after 1 + 3,2 + 3 or direct 3-generation targeted therapy). There is no limit on the number of chemotherapy lines. The enrolled patients required brain parenchyma and extracranial lesion stable - ECOG PS score: 0-3 - Normal main organ function, That is, the following criteria are met: 1. routine blood examination (no blood transfusion within 14 days, no hematopoietic stimulating factor drugs are corrected state): hemoglobin (Hb) 90g / L; Absolute neutrophil count (ANC) 1.5109 / L; Platelet (PLT) 100109 / L; White blood cell count (WBC) 3.0109 / L; 2. Biochemical examination: alanine transaminotransferase (ALT) and alanine transaminotransferase (AST) 2.5 upper limit of normal (ULN); Serum total bilirubin (TBIL) 1.5 ULN; Serum creatinine (Cr) of 1.5 ULN or creatinine clearance of 50 ml/min; If any liver metastasis, Then, the total bilirubin 3 ULN, ALT and AST 5 ULN; C) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time 12 (PT) 1.5 ULN; d) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) 50%; - If previously treated with chemotherapy, A washout period of at least 21 days between the last chemotherapy dose and enrollment (if the patient does not receive radiotherapy) is required; Patients who treated brain parenchymal metastases with local radiotherapy or surgery before enrollment, Must be completed and fully recovered from the acute toxicity of radiotherapy / surgery. A minimum 14-day washout period is required between the end of radiotherapy and enrollment. A minimum 30-day washout period is required between the end of surgery and enrollment. - Expected survival of not less than 3 months - patients can swallow oral medication (if not oral, can be ground by gastric tube) - Women of childbearing age must have negative pregnancy test (serum or urine) within 14 days before observation period and 3 months after the last administration; for men, they should undergo surgical sterilization or agree to use appropriate contraception during the observation period and 3 months after the last administration of study drug - patients voluntarily participate and sign an informed consent (or legal agent), expected to have good compliance and able to cooperate with the study according to the protocol requirements. Exclusion Criteria: - Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the study program; - Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) - patient with active bacterial infection, fungal infection (intravenous antibiotics required at initiation of study treatment); - past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid therapy, Or any signs of clinically active interstitial lung disease; - arterial / venous thrombosis events within 6 months prior to enrollment, Such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; - congestive heart failure (NYHA grade> 2); unstable angina pectoris; a myocardial infarction within 3 months prior to signing an ICF; any 12 supraventricular or ventricular arrhythmia requiring treatment or intervention; Mean QTcF> 470ms from 3 ECG recordings - other systemic malignancies in the last 5 years, (Except for cured skin basal cell carcinoma and cervical situ carcinoma and ovarian carcinoma); - Use drugs or supplements known to be the main cause of CYP3A4. - Persons known to be allergic to any test drug or its excipients; - pregnant, lactating, reproductive patients unwilling to use effective contraception; ●a clear prior history of neurological or psychiatric disorders, including epilepsy and dementia; - other conditions considered inappropriate by the investigator.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Gen Lin

Address:
City: Fuzhou
Country: China

Contact:
Last name: Gen Lin
Email: lingen197505@163.com

Start date: October 1, 2024

Completion date: October 1, 2028

Lead sponsor:
Agency: Fujian Cancer Hospital
Agency class: Other

Source: Fujian Cancer Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06441045