An Investigator-Initiated Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Efficacy of [177Lu]Lu-DOTA-EB-RGD2 in Patients With Recurrent High-grade Glioma
This is an investigator-initiated, Phase I clinical trial. It aims to evaluate the safety, tolerability, dosimetry, and preliminary anti-tumor activity of a novel radiopharmaceutical, \[177Lu\]Lu-DOTA-EB-RGD2, in patients with recurrent high-grade gliomas. Participants will receive the drug either via intravenous infusion or directly into the tumor cavity through a pre-implanted Ommaya reservoir (a subcutaneously placed device that allows direct access to the tumor cavity). The study employs a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD). Adverse events, biodistribution, and tumor response (by MRI) will be assessed. Approximately 24 patients will be enrolled across two major Chinese medical centers: Beijing Tiantan Hospital and Peking Union Medical College Hospital.
• The participant must sign the informed consent form before participation.
• Age ≥ 18 years.
• Histologically confirmed glioblastoma (WHO classification) after surgical resection or biopsy.
• Participants receiving corticosteroids (e.g., dexamethasone) must be on a stable or decreasing dose ≤ 4 mg/day (or equivalent) for at least 7 days before start of study treatment.
• Adequate bone marrow and organ function confirmed by laboratory tests performed ≤ 14 days before first study treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 10.0 g/dL; Serum creatinine ≤ 1.5 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN; albumin ≥ 30 g/L; ALT and AST \< 3 × ULN in absence of liver metastases, or \< 5 × ULN if liver metastases present; Coagulation: activated partial thromboplastin time (APTT) ≤ 2 × ULN, international normalized ratio (INR) ≤ 1.5 (if not receiving anticoagulation therapy);
• Evidence of disease progression (PD) by RANO 2.0 criteria confirming recurrence: ≥ 25% increase in product of perpendicular diameters or \> 40% increase in tumor volume compared to baseline after initial treatment or best response, while on stable or increasing corticosteroid dose. Clinical deterioration or increased corticosteroid dose alone is insufficient. MRI contrast enhancement, MRS, and/or metabolic PET should help differentiate true progression from radiation necrosis/pseudoprogression. Also, at least one bi-dimensionally measurable contrast-enhancing lesion with shortest diameter ≥ 10 mm must be present on MRI.
• For participants receiving Ommaya reservoir implantation for locoregional administration, surgery must be completed at least 2 weeks before first radionuclide therapy, with no postoperative complications. Baseline MRI for efficacy assessment must be performed at least 2 weeks after implantation and before first radionuclide therapy.
• Tumor uptake confirmed by NOTA-PRGD2 PET/CT after diagnosis of recurrence and before radionuclide therapy. For participants with Ommaya reservoir, PET/CT must be performed at least 2 weeks after implantation and before first radionuclide therapy.
• Life expectancy \> 6 months.
⁃ Karnofsky Performance Status (KPS) score ≥ 50.