An Investigator-Initiated Trial to Evaluate the Dosimetry, Safety, Tolerability, and Preliminary Efficacy of a Single-Dose [177Lu]Lu-XT771 Injection in Patients With Recurrent Glioblastoma
The primary objective of this study is to evaluate the dosimetry, safety, and tolerability of the investigational radiopharmaceutical \[177Lu\]Lu-XT771 in patients with recurrent glioblastoma, an aggressive form of brain cancer. \[177Lu\]Lu-XT771 is designed to specifically target and deliver beta radiation directly to tumor cells that overexpress carbonic anhydrase IX and XII (CA IX and CA XII). This early-phase, investigator-initiated trial will enroll a small group of approximately 3-5 patients, each receiving a single dose of \[177Lu\]Lu-XT771. The drug will be administered locoregionally via an implanted Ommaya reservoir, directly into the tumor cavity. Following administration, patients will be closely monitored using single-photon emission computed tomography/computed tomography (SPECT/CT) to assess the biodistribution of the drug and to quantify the absorbed radiation dose to both the tumor and normal organs. The study will also document all adverse events to characterize the safety profile of the treatment and will provide a preliminary assessment of its anti-tumor activity, as measured by progression-free survival. The information gathered from this exploratory study will be used to determine the recommended safe starting dose for future Phase I clinical trials.
• Subject has fully understood the study and voluntarily signed the informed consent form.
• Age ≥ 18 and ≤ 80 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Life expectancy of at least 3 months.
• Histologically confirmed glioblastoma (based on the 2021 WHO Classification of Tumors of the Central Nervous System, 5th edition), and confirmed CA IX/CA XII positive by histology or \[68Ga\]Ga-XT771 PET/CT.
• Histologically confirmed recurrence of glioblastoma following prior treatments.
• Suitable for Ommaya reservoir placement and meets the conditions for drug administration, as judged by the investigator.
• Tumor resection cavity volume between 2.5 and 25 cm\^3.
• On a stable or decreasing dose of corticosteroids (≤5 mg/day of dexamethasone or equivalent) for at least 1 week prior to the first dose.
⁃ Toxicity from prior anti-tumor treatments (e.g., chemotherapy, radiotherapy, immunotherapy) recovered to ≤ Grade 1 (excluding alopecia).
⁃ Adequate organ and bone marrow function meeting the following criteria:
∙ Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 ×10\^9/L and white blood cell (WBC) count ≥ 3 ×10\^9 /L (without growth factor support within 28 days prior to dosing); Platelet count ≥ 75 ×10\^9/L; Hemoglobin ≥ 90 g/L.
‣ Hepatic function: Total bilirubin ≤ 1.5 × ULN (≤ 2.0 × ULN for subjects with liver metastases; ≤ 3.0 × ULN for subjects with confirmed Gilbert's syndrome); ALT and AST ≤ 3 × ULN (\< 5 × ULN for subjects with liver metastases); Albumin \> 30 g/L.
‣ Renal function: Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min.
‣ Coagulation: INR ≤ 2.0, APTT ≤ 1.5 × ULN. (Exception: subjects receiving warfarin may have an INR between 2 and 3 inclusive).
⁃ Fertile subjects (and their partners) must agree to use highly effective contraceptive methods (e.g., condoms, oral or injectable contraceptives) during the treatment period and for 6 months after the last dose of the study drug.