Mechanism study on synergistic radio-protection and sensitization of ginseng-derived nanoparticles based on spatial metabolomics in elderly patients with locally advanced cervical cancer

开始日期2023-06-01

申办/合作机构

苏州大学附属第一医院

EUCTR2021-003774-32-IT

/ Unknown status临床2期IIT

Enhancing Treatment in Persistent Glioblastoma through AGuIX Nanoparticles for Precision Radiotherapy (NanoGBM-Precision): A Phase II, monocenter, open-label, single-arm, no-profit clinical trial. - NanoGBM-Precision

开始日期2022-01-26

申办/合作机构-

NCT04899908

/ Recruiting临床2期IIT

A Double-blind, Phase II Randomized Study of Brain-directed Stereotactic Radiation With or Without AGuIX Gadolinium-based Nanoparticles in the Management of Brain Metastases at Higher Risk of Local Recurrence With Radiation Alone

The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

开始日期2021-09-15

申办/合作机构

Dana-Farber Cancer Institute, Inc.

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100 项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的临床结果

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100 项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的转化医学

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100 项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的专利（医药）

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项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的文献（医药）

2024-11-01·Cancer Radiotherapie

Use of nanoparticles in radiation oncology

Review

作者: Verry, Camille ; Bourbonne, Vincent ; Schick, Ulrike ; Lucia, François

Radiotherapy is a major therapeutic strategy for cancer treatment. Despite many technology advances in the last two decades, local control remains often suboptimal, especially in locally advanced tumours, which are often hypoxic, and radioresistant. In addition, irradiation of surrounding tissues and organs at risk usually precludes further dose escalation to minimize acute and late toxicities. Radiosensitizing agents such as chemotherapies targeting the DNA repair, or targeted monoclonal antibodies (cetuximab) have been shown to improve local control in many tumour types. More recently, radioenhancers have emerged as a new way to overcome the limitations of radiation. Here, we review the state of the art in this field and will focus on the past and ongoing clinical trials with the nanoparticles NBTXR3 and AGuIX®.

2024-09-01·Clinical and Translational Radiation Oncology

NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase 1b outcomes and MRI-based biodistribution

Article

作者: Moreau, J ; Molnar, I ; Lavielle, A ; Boux, F ; Dufort, S ; Le Duc, G ; Biau, J ; Guillemin, F ; Cremillieux, Y ; Leyrat, B ; Seddik, K ; Thivat, E ; Durando, X ; De Beaumont, O

Background:

In glioblastoma (GBM), tumor progression occurs mainly within the irradiated tumor volume. To address this challenge, a radiosensitization strategy with intravenous gadolinium-based theranostic nanoparticles (AGuIX) is being explored in the NANO-GBM phase1b/2R trial (NCT04881032). Here, we present the results of the phase 1b part, which is the first-in-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed GBM.

Material and Methods:

Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed GBM, with incomplete resection (biopsy or partial surgery). The phase 1b part was a dose escalation approach (Time-to-event Continuous Reassessment Method) with three dose levels: 50, 75, and 100 mg/kg. Patients were treated with RT (60 Gy), and concomitant and adjuvant TMZ, and 4 injections of AGuIX (D-3/-7, D1, D8, and D15). Dose-limiting-toxicity (DLT) was defined as any grade 3-4 adverse event (CTCAE v5.0), excluding alopecia, nausea, and rapidly controlled vomiting. Pharmacokinetic (PK), and biodistribution based on MRI were evaluated.

Results:

Between March 2022 and March 2023, eight patients were enrolled: 1 at 50 mg/kg, 1 at 75 mg/kg, and 6 at 100 mg/kg. All patients received the four AGuIX injections. Only one patient experienced a DLT (at 100 mg/kg): a grade 3 lymphopenia (related to TMZ). The RP2D of AGuIX was determined as 100 mg/kg. AGuIX mean AUC increased with dose. Regions of GBM with moderate (36-123 µM), and high (123-291 µM) or very high (>291 µM) AGuIX concentrations accounted in average for 38.7 and 26.8 %, respectively.

Conclusion:

These results confirm the lack of AGuIX-related toxicity and the widespread dispersion of nanoparticles throughout GBM. This supports progression to the randomized phase 2 part, utilizing an RP2D of AGuIX of 100 mg/kg (4 injections).

2024-07-02·ACS Nano

Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer

Article

作者: Gouy, Sébastien ; Ba, Mouhamadou ; Morel, Daphné ; Pautier, Patricia ; Duc, Géraldine L E ; Maury, Pauline ; Bockel, Sophie ; Robert, Charlotte ; Achkar, Samir ; Massard, Christophe ; Genestie, Catherine ; Espenel, Sophie ; Bahleda, Ratislav ; Dufort, Sandrine ; Texier, Matthieu ; Maulard, Amandine ; Lux, François ; Chargari, Cyrus ; Morice, Philippe ; Tillement, Olivier ; Porcel, Erika ; Debeaumont, Olivier ; Deutsch, Eric ; Ammari, Samy

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T₁-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.

项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的新闻（医药）

2024-09-03

·Business Wire

NH TherAguix Announces Continuation of the Phase II NANOBRAINMETS Trial in the Treatment of Brain Metastases after Completion of a Futility Analysis

PARIS--( BUSINESS WIRE )--NH TherAguix (NHT), a phase II clinical-stage biotechnology company specializing in the development of novel nanomedicine solutions for precision radiotherapy in oncology, today announced that the DSMB has validated the continuation of the Phase II trial, NANOBRAINMETS, managed by the Dana Farber Cancer Institute, following the futility analysis scheduled after the enrollment and follow up of 50% of patients in the study. Ongoing evaluation of the study has revealed no serious adverse events related to the administration of AGuIX®, highlighting its very favorable safety profile. Developed by NHT, AGuIX® is designed to improve tumor targeting and increase radiobiological damage to tumor tissue locally. 96 patients have been randomized up to date on the 134 scheduled in the study’s protocol. Next interim analysis is currently expected by the end of 2024 to assess the clinical efficacy of AGuIX ®. Download the full press release in PDF About NH TherAguix: www.nhtheraguix.com NH TherAguix is a Phase 2 biotech company developing AGuIX®, an innovative nano drug to treat tumors and metastases in patients undergoing radiotherapy. Approximately 60% of cancer patients receive radiotherapy. AGuIX®’s pharmacological properties and mode of action by bio-distribution allow it to enhance the radiotherapy precision and effectiveness in the heart of tumours conferring it a pan-cancer potential. AGuIX® is currently being evaluated in multiple Phase II randomized trials across various cancer types such as brain metastases, glioblastoma, and pancreatic and lung cancers. Over 200 patients have currently been treated with AGuIX® with an excellent safety profile and promising preliminary clinical results. AGuIX® is protected by 18 patent families and has been extensively tested in various preclinical models, with results published in more than 80 high-impact, peer reviewed scientific publications.

临床2期

2021-06-10

·GlobeNewswire

WPD Pharmaceuticals Invited to Join International Research

VANCOUVER, British Columbia, June 10, 2021 (GLOBE NEWSWIRE) -- WPD Pharmaceuticals Inc. (CSE: WBIO)(FSE: 8SV1) (the “Company” or “WPD”) a clinical-stage pharmaceutical company, is excited to announce that it has been invited to be a member of an international consortium of leading industry experts researching the potential of AGuIX® nanoparticles in maximizing radiotherapy efficiency. The consortium will also explore two of WPD’s compounds specifically, WP1066 and WP1122, to restore GBM cells' sensitivity to radiotherapy. The consortium is coordinated by Dr. Muriel Barberi-Heyob from CRAN, University de Lorraine, France, and has been successfully funded by EuroNanoMed III "European Innovative Research & Technological Development Projects in Nanomedicine" project – “RXnanoBRAIN Nanoparticles to optimize the effects of radiotherapy of brain tumors: Multi-scale modeling and experimental validation”. Along with WPD Pharmaceuticals’ Dr. Beata Pajak, the consortium includes Oslo University Hospital (Norway) represented by Dr. Kristian Berg, NH TherAguix (France) company represented by Dr. Sandrine Dufort, and Jagiellonian University in Krakow (Poland) represented by Dr. Martyna Elas. Over the three year project timeline, the consortium aims to plan and adapt the X-ray doses given to the patient to maximize radiotherapy efficiency on these high-grade tumors while preserving the adjacent healthy tissue. This project will base its work on pre-clinical experiments at different biological scales (cells, tissues, and in vivo on rodent models) and algorithms' development. An evaluation will then be carried out of the therapeutic potential of an innovative nanoparticle which results from the discovery of NH TherAGuIX and is currently in clinical development. Researchers will study the complementarity and effectiveness of the energy of radiotherapy and nanoparticles (NPs) within tumor tissue. Gaining an in-depth understanding of the effects on the immune response to control and comprehensively enhance the potential of the effects of this treatment also represents a crucial innovative step for the project. Glioblastoma is the most common form of brain cancer and is generally aggressive. The standard treatment consists of surgical removal of the tumor when possible, followed by concurrent radiotherapy and chemotherapy. Radiotherapy has an undisputedly positive role to play after surgery and contributes to improving the overall prognosis of these tumors. However, unfortunately, many patients develop a recurrence of local tumors even when treatment is carried out well. Nanomedicine - and nanoparticles in particular - are the source of excellent prospects for development and innovation in radiotherapy. About WPD Pharmaceuticals WPD is a biotechnology research and development company with a focus on oncology and virology, namely research and development of medicinal products involving biological compounds and small molecules. WPD has licensed in certain countries 10 novel drug candidates with 4 that are in clinical development stage. These drug candidates were researched at medical institutions, and WPD currently has ongoing collaborations with Wake Forest University and leading hospitals and academic centers in Poland. WPD has entered into license agreements with Wake Forest University Health Sciences and sublicense agreements with Moleculin Biotech, Inc. and CNS Pharmaceuticals, Inc., respectively, each of which grant WPD an exclusive, royalty-bearing sublicense to certain technologies of the licensor. Such agreements provide WPD with certain research, development, manufacturing and sales rights, among other things. The sublicense territory from CNS Pharmaceuticals and Moleculin Biotech includes for most compounds 30 countries in Europe and Asia, including Russia. On Behalf of the Board ‘Mariusz Olejniczak’ Mariusz Olejniczak CEO, WDP Pharmaceuticals Contact: Investor Relations Email: investors@wpdpharmaceuticals.com Tel: 604-428-7050 Web: Investor Relations: Arrowhead Business and Investment Decisions, LLC Thomas Renaud Managing Director 42 Broadway, 17th Floor New York, NY 10004 Office: +1 212 619-6889 enquire@arrowheadbid.com Cautionary Statements: Neither the Canadian Securities Exchange nor the Investment Industry Regulatory Organization of Canada accepts responsibility for the adequacy or accuracy of this release. This press release contains forward-looking statements. Forward-looking statements are statements that contemplate activities, events or developments that the Company anticipates will or may occur in the future. Forward-looking statements in this press release include that WPD’s drugs could be developed into novel treatments for cancer. These forward-looking statements reflect the Company’s current expectations based on information currently available to management and are subject to a number of risks and uncertainties that may cause outcomes to differ materially from those projected. Factors which may prevent the forward looking statement from being realized is that the technology may not provide the benefits expected and we may not engage them further; competitors or others may successfully challenge a granted patent and the patent could be rendered void; that we are unable to raise sufficient funding for our research; that we may not meet the requirements to receive the grants awarded; that our drugs don’t provide positive treatment, or if they do, the side effects are damaging; competitors may develop better or cheaper drugs; and we may be unable to obtain regulatory approval for any drugs we develop. The Company assumes no obligation to update them except as required by applicable law.

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100 项与基于聚硅氧烷Gd-螯合物的纳米颗粒相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
结直肠癌	临床2期	美国	NH TherAguix SAS初创企业	2021-09-15
HER2阳性乳腺癌	临床2期	美国	NH TherAguix SAS初创企业	2021-09-15
肺癌	临床2期	美国	NH TherAguix SAS初创企业	2021-09-15
黑色素瘤	临床2期	美国	NH TherAguix SAS初创企业	2021-09-15
Snyder-Robinson综合征	临床2期	美国	NH TherAguix SAS初创企业	2021-09-15
非小细胞肺癌	临床2期	美国	NH TherAguix SAS初创企业	2021-05-27
不能切除性胰腺癌	临床2期	美国	NH TherAguix SAS初创企业	2021-05-27
胰腺导管腺癌	临床2期	美国	NH TherAguix SAS初创企业	2021-05-27
脑转移瘤	临床2期	法国	NH TherAguix SAS初创企业	2019-03-26
宫颈癌	临床1期	法国	NH TherAguix SAS初创企业	2018-11-08

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2012	N/A	胶质母细胞瘤	-	Ultrasmall gadolinium-loaded polymer nanoparticles	淵廠窪鏇範鹽鏇鏇範糧(簾網淵構衊鬱糧鹹憲積) = 壓範餘製鹹壓網淵積選顧糧鏇齋鹽醖選築夢網 (鬱製範鑰鬱艱鹽觸憲憲 )	-	2012-04-15