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Recurrent High-Grade GliomasEarly Phase 1NCT07655869

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

A Early Phase 1 study testing [177Lu]Lu-DOTA-EB-RGD2 in people with Recurrent High-Grade Gliomas and Recurrent Glioblastoma IDH Wildtype, run by Beijing Tiantan Hospital at 2 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
[177Lu]Lu-DOTA-EB-RGD2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesChina
Study dates
1 Jun 2026to 31 Jan 2027
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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);
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  • 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.

Who cannot join

  • 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:
  • Documented myocardial infarction, angina pectoris, cardiomyopathy, symptomatic pericarditis, or coronary artery bypass grafting within 6 months before enrollment.
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  • 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).
  • 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).
  • 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.
  • 6. 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).
  • 7. 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.
  • 8. Use of bevacizumab for glioblastoma or supportive care (e.g., edema reduction) within 60 days before start of study treatment.
  • 9. Patients with disease progression within the first 12 weeks after completion of radiotherapy are excluded from recurrent disease trials.
  • 10. Prior intracranial locoregional drug therapy before [177Lu]Lu-DOTA-EB-RGD2 treatment.
  • 11. 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.
  • 13. Grade 4 myelosuppression from prior anticancer therapy that has not recovered within 2 weeks, or grade 3 myelosuppression requiring >6 weeks to recover.
  • 14. Blood transfusion within 4 weeks before screening to meet eligibility criteria.
  • 15. Known hypersensitivity or delayed allergic reaction to any component of [177Lu]Lu-DOTA-EB-RGD2 or similar drugs.
  • 16. Severe disease of the cardiac, respiratory, central nervous system, renal, hepatic, or other organ systems that, in the investigator's opinion, may increase participant safety risk.
  • 17. Active infection requiring intravenous antibiotics (bacterial, fungal, or viral) within 4 weeks before first dose, or any other uncontrolled active infection deemed clinically significant by the investigator.
  • 18. History of drug or alcohol abuse within one year before screening, long-term drug use, or psychiatric illness that may affect compliance.
  • 19. Participation in another investigational drug or device trial within 4 weeks before first dose.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Li'ao Wang, M.D. contact

+86 15001171671

wangliao17@163.com

Deling Li, M.D. contact

lideling@bjtth.org

China2 sites, 2 recruiting
  • Beijing Tiantan Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100070

    Li'ao Wang, M.D., 15001171671, wangliao17@163.com

    Deling Li, M.D.

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

    Beijing, Beijing Municipality, 100730

    Zhaohui Zhu, M.D., +86 15909835868, 13611093752@163.com

    Zhaohui Zhu, M.D.

    Recruiting

Other trials in China

About this study

Official title: 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.

Read the detailed description

This is a multicenter, open-label, Phase I dose-escalation study with two parallel routes of administration: intravenous (IV) and locoregional (via Ommaya reservoir into the tumor cavity). The primary objective is to determine the maximum tolerated dose (MTD) of [177Lu]Lu-DOTA-EB-RGD2 for each route using a standard "3+3" design. Three dose levels per cycle are planned for each route (IV and locoregional). Treatment is given every 3 weeks for up to 2 cycles, with possible additional cycles based on clinical benefit as judged by the investigator.

Primary endpoint: Dose-limiting toxicity (DLT) incidence during the first 6 weeks (2 cycles), graded by CTCAE v5.0.

Secondary endpoints: Adverse events (type, frequency, severity); time-activity curves and absorbed radiation doses in organs and tumors (based on whole-body planar imaging and SPECT/CT at multiple time points); pharmacokinetic parameters (AUC, Cmax, Tmax, clearance [CL], volume of distribution [Vz], terminal half-life) from blood and urine sampling; objective response rate (ORR) per RANO 2.0 (by contrast-enhanced MRI); overall survival.

Exploratory endpoints: Change in tumor αvβ3 integrin expression by NOTA-PRGD2 PET/CT; correlation between baseline NOTA-PRGD2 PET uptake and treatment response.

Sample size: Approximately 24 patients (up to 3+3 per dose level per route) using the 3+3 rule. No formal hypothesis testing is planned; descriptive statistics will be used.

Study duration: 36 months (recruitment approximately 12 months, treatment and follow-up approximately 24 months). The trial is conducted at Beijing Tiantan Hospital and Peking Union Medical College Hospital, China.

Being tested
[177Lu]Lu-DOTA-EB-RGD2
Keywords
Recurrent High-Grade Gliomas, Integrin αvβ3, Targeted Radionuclide Therapy, Safety and Tolerability, Radiation Dosimetry

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [177Lu]Lu-DOTA-EB-RGD2Drug

    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.

Study groups in NCT07655869
Study groupRoleWhat they receive
Intravenous Administration of [177Lu]Lu-DOTA-EB-RGD2ExperimentalParticipants 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.
Receives: Drug: [177Lu]Lu-DOTA-EB-RGD2
Locoregional Administration of [177Lu]Lu-DOTA-EB-RGD2ExperimentalParticipants 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.
Receives: Drug: [177Lu]Lu-DOTA-EB-RGD2

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (11)
  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.

    Measured: 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.

    Measured: 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.

    Measured: Within 6 weeks (42 days) after the first dose

  4. 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.

    Measured: 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)

  5. Objective Response Rate (ORR)

    Proportion of participants achieving complete response (CR) or partial response (PR) on contrast-enhanced MRI according to RANO 2.0 criteria. CR is defined as disappearance of all enhancing and non-enhancing lesions without new lesions; PR is defined as a ≥50% decrease in the product of perpendicular diameters from baseline.

    Measured: 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)

  6. Overall Survival (OS)

    Time from the first dose of [177Lu]Lu-DOTA-EB-RGD2 to death from any cause. Participants alive at study end or lost to follow-up are censored at their last known alive date.

    Measured: From the first dose up to 17 months (study duration)

  7. Maximum Plasma Concentration (Cmax) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

    Cmax directly observed from concentration-time data, measured from venous blood samples.

    Measured: 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)

  8. Time to Maximum Plasma Concentration (Tmax) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

    Tmax corresponding to Cmax, measured from venous blood samples.

    Measured: 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)

  9. Systemic Clearance (CL) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

    CL calculated as Dose/AUC, measured from venous blood samples.

    Measured: 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)

  10. Volume of Distribution During Terminal Phase (Vz) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

    Vz calculated as CL/λz, measured from venous blood samples.

    Measured: 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)

  11. Terminal Half-Life (t1/2) of [177Lu]Lu-DOTA-EB-RGD2 in Blood

    t1/2 calculated from the terminal phase of the concentration-time curve, measured from venous blood samples.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2026
  2. Study start1 Jun 2026 (estimated)
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Parallel assignment with two arms, each using a 3+3 dose-escalation design.
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07655869
Sponsor's protocol ID
BRWEP2024W032040206
Status last verified
Jun 2026
First submitted
10 Jun 2026
Last updated
18 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: The decision on whether to share individual participant data (IPD) has not yet been finalized. This is a Phase I investigator-initiated trial with a small sample size (approximately 24 participants). Data sharing will be considered in accordance with institutional policies, patient consent, and Chinese regulatory requirements. Any future sharing would require additional ethical approval and a data transfer agreement.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing [177Lu]Lu-DOTA-EB-RGD2 in people with Recurrent High-Grade Gliomas and Recurrent Glioblastoma IDH Wildtype, run by Beijing Tiantan Hospital at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Li'ao Wang, M.D. (+86 15001171671, wangliao17@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-Limiting Toxicities (DLTs) (time frame: Within 6 weeks (42 days) after the first dose (during the first two cycles; each cycle is 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.

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