[177Lu]Lu-DOTA-EB-RGD2 Therapy in Patients With Recurrent High-grade Glioma

NCT07655869 | Recruiting Early Phase 1

• 1 other identifier: BRWEP2024W032040206
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent High-Grade Gliomas; Recurrent Glioblastoma IDH Wildtype

Keywords

Recurrent High-Grade Gliomas; Integrin αvβ3; Targeted Radionuclide Therapy; Safety and Tolerability; Radiation Dosimetry

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-Limiting Toxicities (DLTs)

  DLTs are defined as protocol-specified adverse events occurring during the first 6 weeks (2 cycles) after the first dose, graded by NCI CTCAE v5.0. DLTs include: Grade ≥3 neurological toxicities (e.g., grade 3 CNS necrosis, grade 3 decreased consciousness, grade 3 hydrocephalus, grade 3 seizure, grade 3 headache that lasts over 24 hours with treatments, grade ≥4 cerebral edema); Grade ≥3 hematologic toxicities (e.g., grade 3 febrile neutropenia, grade 3 anemia lasting \>7 days, grade 3 lymphopenia with infection, grade 4 neutropenia lasting \>7 days, grade 4 thrombocytopenia or grade 3 with bleeding); Any grade ≥3 non-hematologic toxicity (except transient grade 3 nausea/vomiting/diarrhea lasting \<3 days, grade 3 fatigue lasting \<1 week, or electrolyte abnormality lasting less than 72 hours and resolved by supportive care); Any Hy's law event (e.g., ALT or AST \> 3-fold upper limit normal); Death or significant clinical intervention related to the study drug.

  Within 6 weeks (42 days) after the first dose (during the first two cycles; each cycle is 21 days)

Secondary Outcomes (11)

• Incidence and severity of adverse events (AEs)

  From the first dose (Day 1) until study completion (up to 17 months)

• Radiation Dosimetry

  From the first dose up to 192 hours (Day 8)

• Maximum Tolerated Dose (MTD)

  Within 6 weeks (42 days) after the first dose

• Area Under the Concentration-Time Curve (AUC) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

  Pre-dose; 5, 15, 30, 60 minutes; 2, 4, 24, 48, 72, 144, 192 hours post-dose (first cycle only; each cycle is 21 days)

• Objective Response Rate (ORR)

  Baseline, Day 22 (±3 days), Day 42 (±7 days), then every 6 weeks until progression, death, or start of new therapy (up to 17 months)

Other Outcomes (1)

• Change in Tumor Uptake of NOTA-PRGD2 on PET/CT

  Baseline (within 42 days before the first dose) and Day 42 (±7 days) after the first dose

Study Arms (2)

Intravenous Administration of [177Lu]Lu-DOTA-EB-RGD2

EXPERIMENTAL

Participants receive \[177Lu\]Lu-DOTA-EB-RGD2 via intravenous infusion 20-30 minutes once every 3 weeks (Q3W) for up to 2 cycles (6 weeks). Dose escalation follows a 3+3 design with three dose levels per cycle. Additional cycles may be given based on clinical benefit.

Drug: [177Lu]Lu-DOTA-EB-RGD2

Locoregional Administration of [177Lu]Lu-DOTA-EB-RGD2

EXPERIMENTAL

Participants receive \[177Lu\]Lu-DOTA-EB-RGD2 directly into the tumor cavity through a previously implanted Ommaya reservoir once every 3 weeks (Q3W) for up to 2 cycles (6 weeks). Dose escalation follows a 3+3 design with three dose levels per cycle. Additional cycles may be given based on clinical benefit.

Drug: [177Lu]Lu-DOTA-EB-RGD2

Interventions

[177Lu]Lu-DOTA-EB-RGD2 DRUG

A long-circulating radiolabeled peptide targeting integrin αvβ3. The radiopharmaceutical consists of an RGD2 peptide conjugated to a DOTA chelator and an albumin-binding (EB) motif, labeled with Lutetium-177 (half-life 6.7 days). It is administered intravenously (20-30 min infusion) or locoregionally via Ommaya reservoir directly into the tumor cavity. The study evaluates safety, tolerability, dosimetry, and preliminary efficacy in recurrent high-grade glioma.

Intravenous Administration of [177Lu]Lu-DOTA-EB-RGD2; Locoregional Administration of [177Lu]Lu-DOTA-EB-RGD2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Receiving any other concurrent treatment for glioblastoma outside this study.
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed from the start of \[177Lu\]Lu-DOTA-EB-RGD2 treatment until 6 months after treatment.
• Refusal to use effective contraception during sexual intercourse from informed consent until 6 months after the last dose of study drug.
• Inability to tolerate imaging procedures, repeated blood sampling, or poor venous access.
• Cardiac dysfunction, clinically significant cardiac disease history, or ECG abnormalities indicating a major safety risk, including:
• (1) Documented myocardial infarction, angina pectoris, cardiomyopathy, symptomatic pericarditis, or coronary artery bypass grafting within 6 months before enrollment.
• (2) Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: (a) risk factors for torsade de pointes (TdP) including uncorrected hypocalcemia, hypokalemia, hypomagnesemia, history of heart failure, or clinically significant/symptomatic bradycardia; (b) use of medications known to prolong the QT interval and/or cause TdP that cannot be discontinued or replaced with a safer alternative (e.g., within 5 half-lives or 7 days before study drug); (c) inability to determine the Fridericia-corrected QT interval (QTcF).
• (3) Clinically significant arrhythmia (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block (e.g., bifascicular block, Mobitz type II, third-degree AV block).
• (4) Resting QTcF ≥ 450 ms (male) or ≥ 460 ms (female). (5) Left ventricular ejection fraction (LVEF) \< 50% by echocardiography. (6) Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, regardless of antihypertensive use.
• \. Other malignancy within 5 years before study drug administration, except adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer after curative surgery, carcinoma in situ after curative surgery, or papillary thyroid cancer after curative surgery (hormonal therapy for non-metastatic prostate or breast cancer allowed).
• \. Abnormal serum virology (HBsAg, T. pallidum antibody, HIV antibody, HCV antibody). Patients with untreated active hepatitis B who are willing to receive anti-HBV therapy during study treatment are allowed; patients with inactive hepatitis B are allowed; patients with inactive hepatitis C (HCV antibody positive but HCV RNA below lower limit of detection) are allowed.
• \. Use of bevacizumab for glioblastoma or supportive care (e.g., edema reduction) within 60 days before start of study treatment.
• \. Patients with disease progression within the first 12 weeks after completion of radiotherapy are excluded from recurrent disease trials.
• \. Prior intracranial locoregional drug therapy before \[177Lu\]Lu-DOTA-EB-RGD2 treatment.
• \. Active intracranial or intratumoral hemorrhage detected by CT/MRI. 12. Seizure within 14 days before start of study treatment; epilepsy or increased intracranial pressure uncontrolled by medication.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (2)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100730, China

RECRUITING

Study Officials

• Deling Li, M.D.

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

• Zhaohui Zhu

  Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li'ao Wang, M.D.

CONTACT

+86 15001171671; wangliao17@163.com

Deling Li, M.D.

CONTACT

lideling@bjtth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Model Details: Parallel assignment with two arms, each using a 3+3 dose-escalation design.

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: June 18, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

CN (2)