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

NCT07841106 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026YL01060
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Purpose:To preliminarily evaluate the efficacy and safety of recombinant human endostatin (Endostar) in the early prophylactic cohort (Cohort A) and late salvage cohort (Cohort B) for radiation-induced brain injury after stereotactic radiosurgery (SRS) in patients with non-small cell lung cancer (NSCLC) brain metastases, with a focus on the improvement rate of peritumoral brain edema.Secondary Purpose:To explore the effects of Endostar treatment on neurological function, quality of life, and survival outcomes in patients with NSCLC brain metastases following SRS; and to evaluate the convenience and compliance of the "72-hour continuous intravenous pump infusion" regimen.

Conditions

Lung Cancer (Non-Small Cell); Radiation; Brain Injury; Brain Edema; Brain Necrosis

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Analyzed by the Kaplan-Meier method. OS is defined as the time from enrollment to death from any cause. Surviving patients are censored at last follow-up.

  From enrollment to death from any cause, assessed up to 60 months.

Secondary Outcomes (5)

• Change in Quality of Life Score Assessed by the EORTC QLQ-BN20

  Baseline and Week 4 post-treatment (4 weeks ± 7 days after the 4th treatment cycle; each cycle is 21 days).

• Incidence and Severity of Adverse Events

  From informed consent form (ICF) signing until 4 weeks after the last dose of study drug; assessed before each treatment cycle (each cycle is XX days), with summary at 4 weeks after the last dose.

• Intracranial Progression-Free Survival (iPFS)

  From enrollment until the date of first documented intracranial progression per RANO-BM or death from any cause, whichever came first, assessed up to 60 months; imaging assessments every 2-3 months.

• Brain edema improvement rate

  At Week 4 post-treatment (4 weeks ± 7 days after the 4th treatment cycle; each cycle is 21 days), i.e., the end-of-treatment assessment visit.

• Neurological Function Improvement Rate Assessed by Focused Neurological Examination

  Baseline and Week 4 post-treatment (4 weeks ± 7 days after the 4th treatment cycle; each cycle is 21 days).

Study Arms (2)

Cohort A (Early Prophylaxis)

EXPERIMENTAL

Inclusion of 23 subjects.

Drug: Recombinant Human Endostatin (Endostar)

Cohort B (Late Salvage Cohort)

EXPERIMENTAL

Inclusion of 26 subjects.

Drug: Recombinant Human Endostatin (Endostar)

Interventions

Recombinant Human Endostatin (Endostar) DRUG

Dosage Regimen: Endostar 210 mg, diluted with normal saline to a total volume, administered via continuous intravenous pump infusion over 72 hours (3 days). Treatment Cycle: Every 3 weeks (21 days) constitutes one cycle, for a total of 4 cycles. Route of Administration: Intravenous infusion (continuous pump infusion). Treatment Timing: Cohort A (early prevention cohort): The first cycle should be initiated within 14 days after stereotactic radiosurgery (SRS). Total Treatment Duration: Approximately 12 weeks (4 cycles, 21 days per cycle).

Cohort A (Early Prophylaxis)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Known allergy to Endostar or any of its excipients.
• Received any other anti-angiogenic therapy within 4 weeks before the first dose.
• 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.
• History of arterial thromboembolic events (e.g., MI, unstable angina, CVA, or TIA) within 6 months before the first dose.
• Symptomatic CHF (NYHA Class ≥ II) or severe arrhythmia requiring treatment.
• 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.
• Urine protein ≥++, or 24-hour urine protein ≥2.0 g.
• 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.
• Contraindications to MRI.
• Pregnant or lactating women.
• 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.
• Poor compliance, and the patient is not expected to complete all necessary treatment and follow-up assessments.

Sponsors & Collaborators

• Jiangmen Central Hospital: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Injuries; Brain Edema

Interventions

Endostatins; endostar protein

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Angiostatic Proteins; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Collagen Type XVIII; Non-Fibrillar Collagens; Collagen; Extracellular Matrix Proteins; Scleroproteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of the Oncology Department

Model Details: This study plans to enroll a total of 49 subjects, with 23 assigned to Cohort A (early prevention cohort) and 26 to Cohort B (late salvage cohort).

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: September 25, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: October 1, 2026

Record last verified: 2026-08