Early Prophylactic Versus Late Salvage Recombinant Human Endostatin in Managing Radiosurgery-Induced Brain Injury for NSCLC Brain Metastases

Korábbi kezelés

• Received any other anti-angiogenic therapy within 4 weeks before the first dose.
• History of arterial thromboembolic events (e.g., MI, unstable angina, CVA, or TIA) within 6 months before the first dose.

Más betegség

• Known allergy to Endostar or any of its excipients.
• Uncontrolled hypertension despite medication (SBP >150 mmHg and/or DBP >100 mmHg).
• History of major bleeding (e.g., hemoptysis, gastrointestinal bleeding) or current active bleeding, bleeding tendency, or coagulation disorder.
• Symptomatic CHF (NYHA Class ≥ II) or severe arrhythmia requiring treatment.
• History of gastrointestinal perforation, active gastrointestinal bleeding, intra-abdominal abscess, or active IBD.
• Symptomatic uncontrolled brain metastasis hemorrhage or obvious intracranial hypertension crisis, as judged by the investigator.

Laborértékek

• Severe hepatic/renal insufficiency: total bilirubin >1.5×ULN; or ALT/AST >2.5×ULN; or serum creatinine >1.5×ULN and CrCl <45 mL/min.
• Any severe acute/chronic medical condition, psychiatric disorder, or laboratory abnormality that may increase risk, interfere with results, or affect the investigator's judgment of the patient's ability to complete the study.

Egyéb

• Urine protein ≥++, or 24-hour urine protein ≥2.0 g.
• Contraindications to MRI.
• Pregnant or lactating women.
• Poor compliance, and the patient is not expected to complete all necessary treatment and follow-up assessments.

• Karnofsky performance status (KPS) score ≥60.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Baseline contrast-enhanced brain MRI confirms 1-15 brain metastases, with a total volume of all lesions <15 mL, and the largest lesion with a maximum diameter ≤4.0 cm or volume ≤10 mL.
• Cohort A: Planned to receive SRS, and baseline MRI shows significant peritumoral edema (edema index >2), where EI = (tumor volume + edema volume) / tumor volume. Cohort B: Radiographic (MRI) evidence of radiation-induced brain edema/necrosis after SRS (usually ≥3 months after SRS).
• Prior or concurrent radiotherapy for extracranial lesions is allowed. Prior TKI, chemotherapy, or immunotherapy is allowed. After enrollment, systemic therapy may be continued or adjusted according to clinical need.
• Within 14 days before study treatment, bone marrow and major organ function must meet the following criteria: ANC ≥1.5×10\^9/L; platelets ≥100×10\^9/L; hemoglobin ≥90 g/L; total bilirubin ≤1.5×ULN; AST and ALT ≤1.5×ULN; serum creatinine ≤1.5×ULN or CrCl ≥45 mL/min; INR ≤1.5; APTT ≤1.5×ULN; urine protein <2+; if urine protein ≥2+, 24-hour urine protein <2 g.
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before enrollment. All patients of reproductive potential must agree to use highly effective contraception during the study and for 6 months after the last dose.
• Patients voluntarily participate, have signed the written informed consent form (ICF), and are expected to comply with and follow all study requirements.