[177Lu]Lu-DOTA-EB-RGD2 Therapy in Patients With Recurrent High-grade Glioma
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorBeijing Tiantan Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
[177Lu]Lu-DOTA-EB-RGD2
DrugA 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.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Intravenous Administration of [177Lu]Lu-DOTA-EB-RGD2Experimental treatment 1 intervention
Group B: Locoregional Administration of [177Lu]Lu-DOTA-EB-RGD2Experimental treatment 1 intervention
Trial outcomes
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.
Time frame
Within 6 weeks (42 days) after the first dose (during the first two cycles; each cycle is 21 days)Secondary outcomes
1
Incidence and severity of adverse events (AEs)
All adverse events (AEs), serious AEs (SAEs), treatment-emergent AEs (TEAEs), and deaths, graded by NCI CTCAE v5.0. Assessment includes changes in vital signs, physical examination, electrocardiogram (ECG), echocardiogram (for participants \>60 years), laboratory tests (hematology, serum chemistry, coagulation, urinalysis), and serum pregnancy test (for females of childbearing potential). AE resolution or progression is tracked throughout follow-up.
Time frame
From the first dose (Day 1) until study completion (up to 17 months)2
Radiation Dosimetry
Time-activity curves (TACs) derived from whole-body planar imaging and SPECT/CT at multiple time points post-injection. Absorbed doses to the tumor and major organs are calculated using the MIRD methodology.
Time frame
From the first dose up to 192 hours (Day 8)3
Maximum Tolerated Dose (MTD)
The highest dose level at which ≤1 of 6 participants experiences a DLT during the first 6 weeks (2 cycles), determined separately for the intravenous and locoregional administration arms using the 3+3 dose-escalation design.
Time frame
Within 6 weeks (42 days) after the first dose4
Area Under the Concentration-Time Curve (AUC) of [177Lu]Lu-DOTA-EB-RGD2 in Blood
AUC calculated from time zero to last measurable time point and/or to infinity, measured from venous blood samples.
Time frame
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)Other outcomes
1
Change in Tumor Uptake of NOTA-PRGD2 on PET/CT
Changes in tumor SUVmax, SUVmean, and tumor-to-background ratio (TBR) from baseline to post-treatment PET/CT scans, as an exploratory biomarker of target engagement.
Time frame
Baseline (within 42 days before the first dose) and Day 42 (±7 days) after the first doseSponsors and contacts
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Source ClinicalTrials.gov