Rationale:
To track performance of intravitreal distribution of anti-VEGF-A (Bevazicumab-800CW) and provide information about neovascularization and inflammation in Age-Related Macular Degeneration (AMD), thereby predicting progression and optimizing treatment
Objective:
To determine the safety and feasibility of fluorescence imaging of the eye with the fluorescent tracer bevacizumab-800CW for identification AMD with scanning laser angiography
Study design:
A non-randomized, non-blinded, prospective, single-center feasibility study.
Study population:
Patients group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal.
Control group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal
Intervention (if applicable):
Intravenous injection of bevacizumab-800CW in the patient group.
Main study parameters/endpoints:
Safety and feasibility of the intravenous tracer bevacizumab-800CW in patients with naïve wet AMD and wet AMD by observing the uptake in retinal, choroid and neovascular tissue.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: No risk described in other (running) studies on intravenous injection with bevacizumab-800 CW. Patients need to come back 48-96 hours after injection and the eye measurements take about half an hour longer.
There is no benefit with participation.

开始日期2022-10-28

申办/合作机构

University Medical Center Groningen

NCT06095362 / Completed临床1期

Thyroid Cancer and Lymph Node Metastases Detection Using Bevacizumab-IRDye800CW With Molecular Fluorescence Guided Surgery. Thyroid cAncer Surgery With Intraoperative Molecular fluoRescent Imaging to rEduce overtreatmenT and Morbidity

Background: Papillary thyroid cancer (PTC) patients often develop central lymph node metastases (CLNM), which pose a high risk of disease recurrence. The prophylactic central lymph node dissection (PCLND) is controversial, with proponents arguing for it to prevent local recurrence, and opponents objecting to the hypoparathyroidism and nerve damage risk. Currently, no diagnostic tool exists to identify patients who would benefit from a PCLND. Molecular Fluorescence Guided Surgery (MFGS) is a potential solution that uses fluorescent tracers to detect cancerous tissue. This study aims to investigate whether the administration of a GMP-produced near infrared (NIR) tracer, bevacizumab-IRDye800CW, targeting VEGF-A, can enable intraoperative selection of PTC/FTC/HTC patients for CLND.
Objective: The primary objective of the study is to determine the optimal dose of bevacizumab-IRDye800CW for an adequate tumor-to-background ratio (TBR) in PTC/FTC/HTC lymph node metastases. The secondary objectives are to evaluate the feasibility of MFGS for PTC/FTC/HTC and nodal metastasis assessment, to correlate and validate fluorescence signals detected in vivo with ex vivo histopathology and immunohistochemistry, to evaluate the distribution of bevacizumab-IRDye800CW on a microscopic level, and to quantify the sensitivity and specificity of bevacizumab-IRDye800CW for PTC/FTC/HTC and nodal metastasis.
Study Design: The TARGET-BEVA study is a non-randomized, non-blinded, prospective, single-center phase I feasibility study for patients with confirmed PTC/FTC/HTC, for which the best TBR dosage group in PTC/FTC/HTC nodal metastasis will be determined. The study will initiate with a 3 x 3 scheme: 4,5 mg, 10 mg, and 25 mg, with three patients confirmed with lymph node metastasis in each group. Dosages will be based on previous studies, with the primary objective being the detection of lymph node metastasis. After the first 9 patients, an interim analysis will be performed, after which the best dosage group will be expanded with another 7 patients.
Conclusion: The study aims to identify a novel diagnostic tool that can aid clinicians in selecting patients for PCLND, enabling a reduction in overtreatment, morbidity, and costs while maintaining effectiveness with a lower recurrence rate and improved quality of life.

开始日期2021-11-29

申办/合作机构

University Medical Center Groningen

[+1]

NL-OMON25431 / RecruitingN/AIIT

Fluorescence guided surgery for intra-operative detection of meningioma using Bevacizumab-IRDye800CW: A single center phase I/II study

开始日期2021-08-20

申办/合作机构-

100 项与 Bevacizumab-IRDye800CW(University of Groningen) 相关的临床结果

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100 项与 Bevacizumab-IRDye800CW(University of Groningen) 相关的转化医学

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100 项与 Bevacizumab-IRDye800CW(University of Groningen) 相关的专利（医药）

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项与 Bevacizumab-IRDye800CW(University of Groningen) 相关的文献（医药）

2024-07-01·JOURNAL OF NEUROSURGERY

Bevacizumab-IRDye800CW for tumor detection in fluorescence-guided meningioma surgery (LUMINA trial): a single-center phase I study

Article

作者: Donthu, Venkata Sasank ; Kruijff, Schelto ; Groen, Rob J. M. ; Cordia, Quirine C. F. ; Kruyt, Frank A. E. ; Meersma, Gert Jan ; Dijkstra, Bianca M. ; den Dunnen, Wilfred F. A. ; Nagengast, Wouter B. ; Nonnekens, Julie

OBJECTIVE:

Meningiomas are one of the most frequently occurring brain tumors and can be curatively treated with gross-total resection. A subtotal resection increases the chances of recurrence. The intraoperative identification of invisible tumor remnants by using a fluorescent tracer targeting an upregulated biomarker could help to optimize meningioma resection. This is called molecular fluorescence-guided surgery (MFGS). Vascular endothelial growth factor α (VEGFα) has been identified as a suitable meningioma biomarker and can be targeted with bevacizumab-IRDye800CW.

METHODS:

The aim of this prospective phase I trial was to determine the safety and feasibility of bevacizumab-IRDye800CW for MFGS for intracranial meningiomas by administering 4.5, 10, or 25 mg of the tracer 2–4 days prior to surgery. Fluorescence was verified during the operation with the standard neurosurgical microscope, and tissue specimens were postoperatively analyzed with fluorescence imaging systems (Pearl and Odyssey CLx) and spectroscopy to determine the optimal dose. Uptake was compared in several tissue types and correlated with VEGFα expression.

RESULTS:

No adverse events related to the use of bevacizumab-IRDye800CW occurred. After two interim analyses, 10 mg was the optimal dose based on ex vivo tumor-to-background ratio. Although the standard intraoperative imaging revealed no fluorescence, postoperative analyses with tailored imaging systems showed high fluorescence uptake in tumor compared with unaffected dura mater and brain. Additionally, tumor invasion of the dura mater (dural tail) and invasion of bone could be distinguished using fluorescence imaging. Fluorescence intensity showed a good correlation with VEGFα expression.

CONCLUSIONS:

Bevacizumab-IRDye800CW can be safely used in patients with meningioma; 10 mg bevacizumab-IRDye800CW provided an adequate tumor-to-background ratio. Adjustments of the currently available neurosurgical microscopes are needed to achieve visualization of targeted IRDye800CW intraoperatively. A phase II/III trial is needed to methodically investigate the benefit of MFGS with bevacizumab-IRDye800CW for meningioma surgery in a larger cohort of patients.

2023-05-01·Journal of neurosurgery

Feasibility of bevacizumab-IRDye800CW as a tracer for fluorescence-guided meningioma surgery

Article

作者: Dijkstra, *Bianca M. ; Nagengast, Wouter ; Meersma, Gert Jan ; den Dunnen, Wilfred F. A. ; Kruyt, Frank A. E. ; Groen, Rob J. M. ; Kruijff, Schelto ; Nonnekens, Julie

OBJECTIVE:

Meningiomas are frequently occurring, often benign intracranial tumors. Molecular fluorescence can be used to intraoperatively identify residual meningioma tissue and optimize safe resection; however, currently no clinically approved agent is available for this specific tumor type. In meningiomas, vascular endothelial growth factor α (VEGFα) is upregulated, and this biomarker could be targeted with bevacizumab-IRDye800CW, a fluorescent agent that is already clinically applied for the resection of other tumors and neoplasms. Here, the authors investigated the feasibility of using bevacizumab-IRDye800CW to target VEGFα in a CH-157MN xenografted mouse model.

METHODS:

Five mice with CH-157MN xenografts with volumes of 500 mm3 were administered intravenous bevacizumab-IRDye800CW. Mice were imaged in vivo at 24 hours, 48 hours, and 72 hours after injection with the FMT2500 fluorescence imaging system. Biodistribution was determined ex vivo using the Pearl fluorescent imager at 72 hours after injection. To mimic a clinical scenario, 2 animals underwent postmortem xenograft resection using both white-light and fluorescence guidance. Lastly, fresh and frozen human meningioma specimens were incubated ex vivo with bevacizumab-IRDye800CW, stained with anti-VEGFα, and microscopically examined.

RESULTS:

In vivo, tumors fluoresced at all time points after tracer administration and background fluorescence decreased with time. Ex vivo analyses of tracer biodistribution showed the highest fluorescence in resected tumor tissue. Brain, skull, and muscle tissue showed very low fluorescence. Microscopically, fluorescence was observed in the cytoplasm and was correlated with VEGFα expression patterns. During postmortem surgery, both the tumor bulk and a small tumor remnant were detected. Bevacizumab-IRDye800CW bound specifically to all tested human meningioma samples, as indicated by a high fluorescent signal in the tumor bulk compared with the surrounding healthy dura mater.

CONCLUSIONS:

Bevacizumab-IRDye800CW showed meningioma specificity, as illustrated by high VEGFα-mediated uptake in the meningioma xenograft mouse model. Small tumor lesions were detected using fluorescence guidance. Thus, the next step will be to assess the feasibility of using already available clinical grade bevacizumab-IRDye800CW to optimize meningioma resection in a human trial.

2023-01-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Intraoperative Molecular Fluorescence Imaging of Pancreatic Cancer by Targeting Vascular Endothelial Growth Factor: A Multicenter Feasibility Dose-Escalation Study

Article

作者: Mulder, Babs G Sibinga ; van Dam, Gooitzen M ; Bonsing, Bert A ; Pranger, Bobby K ; Mieog, J Sven D ; Meijer, Vincent E de ; Koller, Marjory ; Burggraaf, Jakobus ; Duiker, Evelien W ; Sarasqueta, Arantza Farina ; Vahrmeijer, Alexander L ; Hoogwater, Frederik J H

Tumor visualization with near-infrared fluorescence (NIRF) imaging might aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor A. The aim of this study was to determine whether intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Methods: In this multicenter dose-escalation phase I trial, patients in whom pancreatic ductal adenocarcinoma (PDAC) was suspected were administered bevacizumab-800CW (4.5, 10, or 25 mg) 3 d before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated with histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma, and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was nonconclusive. Ex vivo TBRs were 1.3, 1.5, and 2.5 for the 4.5-, 10-, and 25-mg groups, respectively. Conclusion: NIRF-guided surgery in patients with suspected PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer than bevacizumab-IRDye800CW for PDAC is preferred.

项与 Bevacizumab-IRDye800CW(University of Groningen) 相关的新闻（医药）

2023-06-25

·生物谷

科学家发现短波红外成像可实现神经母细胞瘤的高对比度荧光引导手术

神经母细胞瘤（neuroblastoma，NB）是儿童最常见的颅外实体肿瘤，占儿童恶性肿瘤的8-10%，约占儿童群体癌症相关死亡的15%。NB浸润性生长的特性使外科医生难以准确识别肿瘤边缘进行最大程神经母细胞瘤（neuroblastoma，NB）是儿童最常见的颅外实体肿瘤，占儿童恶性肿瘤的8-10%，约占儿童群体癌症相关死亡的15%。NB浸润性生长的特性使外科医生难以准确识别肿瘤边缘进行最大程度切除。二醛糖苷抗原（GD2）已被报道在NB中上调，这使得它成为特异性NB成像的一个潜在靶点。来自伦敦大学学院等单位的研究团队，通过构建GD2分别与两种近红外染料（IRDye800CW和IR12）连接的近红外探针荧光引导NB患者手术切除，从而实现NB根治性切除。该研究成果发表在《Cancer Research》期刊上，题目为“Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma”。荧光引导手术将在儿科肿瘤的术中治疗中发挥关键作用。短波红外成像（short-wave infrared imaging，SWIR）比传统的近红外I区（near-infrared window I，NIR-I）成像具有更少的组织散射和自体荧光优势。本研究将两种NIR-I染料（IRDye800CW和IR12），其长尾部分发射在SWIR范围内，与临床级抗GD2单克隆抗体结合，比较NIR-I和SWIR成像在神经母细胞瘤手术中的应用。使用组织模拟样品（已知几何和材料组成的成像标本）评估NIR-I/SWIR设备的灵敏度和深度穿透能力，显示最小可检测体积为~0.9 mm3，深度穿透能力达到3 mm。在体内，使用NIR-I/SWIR设备进行荧光成像，两种染料均显示出高的肿瘤与背景比（tumor-background ratio，TBR），其中，抗GD2-IR800比抗GD2-IR12明显更亮。关键是，该系统使SWIR波长的TBR比NIR-I波长更高，验证了SWIR成像使肿瘤边缘高对比度描绘成为可能。该研究证明，将抗GD2抗体的高特异性与现有NIR-I染料的可用性和可转化性以及SWIR在深度和肿瘤信号与背景比方面的优势相结合，GD2靶向的NIR-I/SWIR引导手术可能有助于改善神经母细胞瘤患者的治疗，并值得开展进一步临床研究。

临床结果临床研究

100 项与 Bevacizumab-IRDye800CW(University of Groningen) 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
克拉茨金瘤	临床2期	荷兰	University Medical Center Groningen	2019-04-01
软组织肉瘤	临床2期	荷兰	University Medical Center Groningen	2018-05-01
乳腺癌	临床2期	-	University of Groningen	-
胰腺癌	临床2期	-	University of Groningen	-
年龄相关性黄斑变性	临床1期	荷兰	University Medical Center Groningen	2022-10-28
甲状腺癌	临床1期	荷兰	University Medical Center Groningen	2021-11-29
垂体腺瘤	临床1期	荷兰	University Medical Center Groningen	2020-10-28
脓毒性休克	临床1期	荷兰	University Medical Center Groningen	2020-10-28
局部晚期食管鳞状细胞癌	临床1期	荷兰	University Medical Center Groningen	2018-10-29
发育不良	临床1期	荷兰	University Medical Center Groningen	2014-04-01