[177Lu]Lu-NeoB for Glioblastoma
Recruiting in Palo Alto (17 mi)
+15 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Novartis Pharmaceuticals
Must not be taking: QT-prolonging drugs
Disqualifiers: Cardiac disease, Other malignancy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This study will investigate different doses of \[177Lu\]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed glioblastoma, with methylated or unmethylated promoter, to assess the safety and efficacy of \[177Lu\]Lu-NeoB in combination with the SoC and in recurrent glioblastoma as single agent, to identify the recommended dose and to also explore the safety of the PET imaging agent \[68Ga\]Ga-NeoB and characterize its uptake in the tumor area.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it mentions that if you are on corticosteroids like dexamethasone, you must be on a stable dose of 4 mg/day or less for at least 7 days before starting the study treatment. Also, if you are taking medications that affect the heart's QT interval, you may need to stop or replace them with safer alternatives.
What data supports the effectiveness of the treatment [177Lu]Lu-NeoB for glioblastoma?
Research on similar treatments, like [177Lu]Lu-DOTATATE and [177Lu]-DOTA-Octreotate, shows that lutetium-177 can be effective in targeting cancer cells, as it is used in treating neuroendocrine tumors and meningiomas. Additionally, a pilot study on glioblastoma using a different lutetium-177 therapy showed promise in improving tumor control.12345
Is [177Lu]Lu-NeoB safe for use in humans?
What makes the drug [177Lu]Lu-NeoB unique for treating glioblastoma?
Eligibility Criteria
This trial is for adults with newly diagnosed or recurrent glioblastoma. Participants must have stable organ and bone marrow function, a Karnofsky performance status of at least 60%, and be able to give informed consent. They should not have severe liver issues (with specific lab value limits) and if on steroids, they need to be on a low dose for at least a week before the study.Inclusion Criteria
You must voluntarily agree to participate in the study after being fully informed of all relevant information.
My diagnosis of Glioblastoma was confirmed through surgery or biopsy.
My recent tests show my organs and bone marrow are functioning well.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants with newly diagnosed glioblastoma receive [177Lu]Lu-NeoB in combination with RT and TMZ every 4 weeks for 6 administrations, with up to 4 additional doses if tolerated. Recurrent glioblastoma participants receive [177Lu]Lu-NeoB as a single agent every 3 weeks for 6 administrations, with up to 4 additional doses if tolerated.
24-40 weeks
Weekly safety and efficacy assessments
Follow-up
Participants are monitored for safety, progression of disease, and survival after treatment
Up to 5 years
Regular visits every 8 weeks for MRI assessments
Treatment Details
Interventions
- [177Lu]Lu-NeoB (Radiopharmaceutical)
- [68Ga]Ga-NeoB (Imaging Agent)
Trial Overview[177Lu]Lu-NeoB in combination with radiation therapy (RT) and Temozolomide (TMZ) is being tested in new glioblastoma cases, while [177Lu]Lu-NeoB alone is tested in recurrent cases. The study also examines the safety of PET imaging agent [68Ga]Ga-NeoB and its uptake in tumors.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: [177Lu]Lu-NeoB in Combination with Radiotherapy (RT) and Temozolomide (TMZ)Experimental Treatment3 Interventions
In newly diagnosed glioblastoma
Group II: [177Lu]Lu-NeoB as Single AgentExperimental Treatment2 Interventions
In recurrent glioblastoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Hospitals Cleveland Medical Center Univ. Hospitals of ClevelandCleveland, OH
University of Colorado DenverAurora, CO
University Hospitals Cleveland Medical CenterCleveland, OH
Uni of Utah Huntsman Cancer InstSalt Lake City, UT
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. [2019]Label="OBJECTIVE" NlmCategory="OBJECTIVE">Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy.
p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">Molecular radiotherapy is a treatment modality that is highly suitable for targeting micrometastases and [177Lu]Lu-DOTATATE is currently being explored as a potential novel treatment option for high-risk neuroblastoma. p53 is a key player in the proapoptotic signalling in response to radiation-induced DNA damage and is therefore a potential target for radiosensitisation.
Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy. [2021]Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [225Ac]Ac-DOTA-SP therapy.
First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control.
In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. [2020]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as "No Carrier Added" (NCA) 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA-(Tyr3)-octreotate with NCA 177Lu ("NCA-LuTATE") and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB) and quantitative 3D SPECT (qSPECT) 177Lu imaging.
A review of advances in the last decade on targeted cancer therapy using 177Lu: focusing on 177Lu produced by the direct neutron activation route. [2023]Lutetium-177 [T½ = 6.76 d; Eβ (max) = 0.497 MeV; maximum tissue range ~2.5 mm; 208 keV γ-ray] is one of the most important theranostic radioisotope used for the management of various oncological and non-oncological disorders. The present review chronicles the advancement in the last decade in 177Lu-radiopharmacy with a focus on 177Lu produced via direct 176Lu (n, γ) 177Lu nuclear reaction in medium flux research reactors. The specific nuances of 177Lu production by various routes are described and their pros and cons are discussed. Lutetium, is the last element in the lanthanide series. Its chemistry plays a vital role in the preparation of a wide variety of radiopharmaceuticals which demonstrate appreciable in vivo stability. Traditional bifunctional chelators (BFCs) that are used for 177Lu-labeling are discussed and the upcoming ones are highlighted. Research efforts that resulted in the growth of various 177Lu-based radiopharmaceuticals in preclinical and clinical settings are provided. This review also summarizes the results of clinical studies with potent 177Lu-based radiopharmaceuticals that have been prepared using medium specific activity 177Lu produced by direct neutron activation route in research reactors. Overall, the review amply demonstrates the practicality of the medium specific activity 177Lu towards formulation of various clinically useful radiopharmaceuticals, especially for the benefit of millions of cancer patients in developing countries with limited reactor facilities.
Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC. [2021]Label="INTRODUCTION">PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties.
A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma. [2021]The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma.
Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹⁷⁷Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic. Recently, a second market authorization in the field was obtained for [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto®) in the treatment of prostate cancer. The efficacy of 177Lu radiopharmaceuticals are now quite well-reported and data on the safety and management of patients are needed. This review will focus on several clinically tested and reported tailored approaches to enhance the risk-benefit trade-off of radioligand therapy. The aim is to help clinicians and nuclear medicine staff set up safe and optimized procedures using the approved 177Lu based radiopharmaceuticals.
Production logistics of 177Lu for radionuclide therapy. [2019]Owing to its favourable decay characteristics 177Lu [T(1/2)=6.71 d, Ebeta(max)=497 keV] is an attractive radionuclide for various therapeutic applications. Production of 177Lu using [176Lu (n,gamma)177Lu] reaction by thermal neutron bombardment on natural as well as enriched lutetium oxide target is described. In all, approximately 4 TBq/g (108 Ci/g) of 177Lu was obtained using natural Lu target after 7 d irradiation at 3 x 10(13) n/cm2/s thermal neutron flux while it was approximately 110 TBq/g (3000 Ci/g) of 177Lu when 60.6% enriched 176Lu target was used. In both the cases, radionuclidic purity was approximately 100%, only insignificant quantity of 177mLu [T(1/2)=160.5 d, Ebeta(max)=200 keV] could be detected as the radionuclidic impurity. Production logistics using different routes of production is compared. Possible therapeutic applications of 177Lu are discussed and its merits highlighted by comparison with other therapeutic radionuclides.
Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma. [2023]Prostate-specific membrane antigen (PSMA) is expressed on the neovasculature as well as to some extent on the glioblastoma cells. With this background, we report the case of a 34-year-old man with recurrent glioblastoma who was treated with 2 cycles of low-dose [ 177 Lu]Lu-PSMA after exhausting all available treatment options in the state sector. Baseline imaging demonstrated intense PSMA signal in the known lesion, which was amenable to therapy. The prospect of [ 177 Lu]Lu-PSMA-based therapy for glioblastoma is warranted going forward.