Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Patients with primary Choroidal Melanoma and Indeterminate Lesions who have received belzupacap sarotalocan (bel-sar; AU-011) in a previous Aura sponsored clinical trial

Patients who are planned to receive plaque radiotherapy for the treatment of IL/CM based on the expert judgment of the investigator

Standard of Care

AU-011

Medical Monitor

This is a prospective multicenter, group-matched study of patients with primary indeterminate lesions or choroidal melanoma who receive treatment with belzupacap sarotalocan (bel-sar; AU-011) and patients who are planned to receive standard of care (SOC) treatment with plaque radiotherapy (plaque) to compare the visual outcomes of AU-011 and plaque radiotherapy.

Up to approximately 45 patients who are planned to receive plaque radiotherapy for the treatment of IL/CM based on the expert judgment of the Investigator are planned to be enrolled.

Prospective Group-Matched Study With Belzupacap Sarotalocan (Bel-sar; AU-011) or Plaque Radiotherapy for Primary Indeterminate Lesions or Choroidal Melanoma (IL/ CM)

A Prospective Group-Matched Study of Visual Outcomes in Subjects Treated With Belzupacap Sarotalocan (AU-011) or Plaque Radiotherapy for Primary Indeterminate Lesions or Choroidal Melanoma (IL/ CM)

Change from baseline in logMAR visual acuity score at 5 years.

Aura Biosciences

Nervous System Diseases

Gland and Hormone Related Diseases

Eye Diseases

Symptoms and General Pathology

Adenoma

Pituitary Diseases

Vision, Low

Pituitary Neoplasms

Vision Disorders

Neoplasms, Glandular and Epithelial

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Sensation Disorders

Neurologic Manifestations

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Patients with visual impairment caused by chiasma compression from sellar area tumors will undergo the following examinations: resting state fMRI, visual tasking state fMRI, diffusion tensor imaging (DTI), visual acuity and automated visual field test.

Volunteers with no visual impairment(visual acuity of both eyes \>1.0) or Nervous System disease will undergo the following examinations: resting state fMRI, visual tasking state fMRI, diffusion tensor imaging (DTI), visual acuity and automated visual field test.

resting state fMRI

Using visual task stimulation to identify the activation characteristic of primary visual cortex.

visual tasking state fMRI

Define the integrity of white matter fibers in the visual pathway.

diffusion tensor imaging

Identify the existence and type of visual field defect.

automated visual field

Assess the visual acuity by using ETDRS scales.

visual acuity

Liu Z Xiong, MD/PhD

Zhong W Ming, MD

Sellar area tumors such as pituitary adenoma, craniopharyngioma and meningioma, etc, commonly lead to visual impairment symptoms. Patients suffer from a loss of visual acuity (VA) and visual field defects (VF) due to a local compression on the optic chiasma by the tumor. In the management of these patients, it is an important goal to evaluate their visual function throughout the treatment, so as to predict the outcome of the visual function .

Since the visual pathway contains a huge complex network of both structure and function, traditional simplex evaluation of VA and VF is obviously not enough. Former studies have revealed changes in the visual network and cortex structure in neurodegenerative diseases and optic neuritis, yet the functional and structural changes caused by local tumor compression and their relation to the visual cortex activity patterns needs further research.

The objective of this research is to asses the visual function in patients with sellar area tumor 1 week preoperatively (baseline),72 hours postoperatively(checking point 1) and at 3 months follow up(checkpoint 2). By using multimodal evaluation including visual resting and task state fMRI, diffusion tensor imaging (DTI), etc. The investigators aim to reveal the changes in functional connectivity (FC), amplitude of low frequency fluctuation (ALFF), regional homogeneity (REHO) ,visual cortex activity patterns and tract-based spatial statistics (TBSS).

Detailed Description:

Study objective

Visual pathway contains both structural and functional network. When it is impacted by neurodegenerative diseases, neuritis or direct mechanical pressure, visual impairment occurs due to damage to the pathway. Former study on Parkinson's disease (Dagmar H. Heep et al, Radiology, 2017 ) found loss of functional connectivity in posterior and paracentral brain regions, while a study on optic neuritis (Yael Backner et al, JAMA Neurology,2018) showed an increase in functional connectivity and slightly loss in optic fiber integrity. Instead of simplex resting-state fMRI，the investigators of this study aim to assess:

1. whether similar changes in functional networking occur when visual pathway is impacted by chiasma compression from tumors in sellar area (by resting-state fMRI).
2. The correlation between local chiasma compression and visual cortex activation pattern ( by visual tasking-state fMRI).
3. Changes and recovery of the white matter fiber structure in the visual pathway.

( by diffusion tensor imaging, DTI).

Method Participants: 60 adult participants (18-60 years old ) will be enrolled in the department of Neurosurgery at Xiangya Hospital of Central South University. The experimental arm will consist of 30 patients with visual impairment symptoms caused by chiasma compression by sellar area tumors (Tumor Group, TG). The control arm will consist of 30 healthy controls without any nervous system disease or visual impairment (Healthy Control Group, HC, control arm).

Study design: Transversal and Longitudinal, single center, comparative study is designed to evaluate functional and structural visual networking of sellar area tumor patients and healthy controls. The study involves assessment with resting-state fMRI, tasking-state fMRI and DTI. Patients of experimental arm will be evaluated by multimodal fMRI at 3 different checkpoints (baseline is 1 week preoperative ,checkpoint 1 is 72 hours postoperative ,checkpoint 2 is 3 months follow up ). Participants of control arm will be evaluated only once. Transversal comparison will be conducted between preoperative tumor patients and healthy controls, while longitudinal comparison will be within tumor group at baseline and two other different checkpoints.

MRI data acquisition and analysis strategy: In this study, the MRI data is acquired by Siemens 3.0T Prisma scanner, including sequences of mprage T1 , diffusion tensor imaging, resting-state fMRI and visual stimulation task fMRI. Resting-state fMRI longitudinal data analysis includes functional connectivity (FC), amplitude of low frequency fluctuation (ALFF) and regional homogeneity (REHO) to assess visual functional networking in both group. These Data wil be analysed using a multivariate approach and independent component analysis (ICA). Visual tasking fMRI will be conducted under classic black and white "chess board" simulation on each eye. For the evaluation of structural visual network, afferent visual pathway (optic tract and radiation ), fiber tracking as well as tract-based spatial statistics (TBSS) will be analyzed within both arms at baseline,checkpoint 1 and checkpoint 2 of the experimental arm will verify changing and recovering process of the visual pathway after chiasma decompression.

Primary outcomes

1. The difference in visual pathway anatomy and functional network between preoperative sellar area tumor patients and healthy controls. Tumor patients will be evaluated clinically by visual acuity (VA), visual field (VF), tumor height and chiasma thickness.
2. The verification of the correlation between patterns of chiasma compression and visual cortex activity. Revealing the difference of visual cortex activity patterns between both arms.

Secondary outcomes Throughout the 3 months follow up of the experimental arm patients, observe and verify the recovery process of both functional and structural visual network after chiasma decompression and evaluate its correlation with clinical visual function outcome.

Statistics

1. An analysis of two sample T test between the two groups will be performed to assess the difference of FC,REHO,ALFF and visual cortex activity pattern between resting state data and data from the visual task of TG and HC.
2. An analysis of variance (ANOVA) within TG group will be performed to assess the changes and recovery of FC, REHO, ALFF and visual cortex activity pattern via resting state data and data from the visual task's data.

Correlations will be explored between multimodal fMRI parameters (both functional and structural) and clinical criteria (e.g VA,VF, tumor size, visual outcome, etc).

Clinical Study of Structural and Functional Evaluation of the Visual Pathway

Multimodal Evaluation on Visual Pathway Predicts the Surgical Curative Effects in Sellar Area Tumors

Outcomes of visual resting state fMRI to assess the functional connectivity (FC) of visual resting network.

Outcomes of visual BOLD fMRI to assess the function of visual cortex by measuring the signal strength (T-test score) of the visual cortex activation.

Outcomes of tract-based spatial statistics (TBSS) to assess the integrity of the white matter fibers in the posterior visual pathway.

Outcomes of visual acuity test for evaluation of the visual function impairment and recovery.

Visual Field Defects via Humphrey visual field chart, Mean Deviation and Standard Deviation in the patients' group at different checkpoints.

Visual resting state fMRI data will be analysed to assess the ALFF data of visual resting network

Outcomes of visual resting state fMRI to assess the regional homogeneity (REHO) of visual resting network.

Outcomes of fractional atrophy (FA) on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.

Outcomes of axial diffusivity (AD) value on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.

Outcomes of radial diffusivity (RD) value on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.

Xiangya Hospital of Central South University

Heart and Blood Diseases

Behaviors and Mental Disorders

Nutritional and Metabolic Diseases

Neoplasm Metastasis

Hemorrhage

Diabetic Retinopathy

Blood Loss, Surgical

Retinal Detachment

Retinal Diseases

Vitreous Hemorrhage

Conversion Disorder

Dissociative Disorders

Neoplastic Processes

Diabetic Angiopathies

Vascular Diseases

Diabetes Mellitus

Diabetes Complications

Mental Disorders

Psychotic Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Pharmaceutical Solutions

Anti-Infective Agents

Blood Substitutes

Micronutrients

Bevacizumab

Lidocaine

Povidone-Iodine

Povidone

Iodine

Cadexomer iodine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Intravitreal bevacizumab Small-gauge pars plana vitrectomy

A sterile lid speculum is used to separate the lids. A subconjunctival injection of 1% lidocaine is applied to the inferotemporal quadrant. A 5% povidone iodine solution is used to disinfect the entire conjunctival surface. 1.25 mg / 0.05 mL of bevacizumab is injected using a 30-gauge needle inserted through the inferotemporal pars plana 3.5 mm from the limbus.

Intravitreal bevacizumab

Small-gauge pars plana vitrectomy

The purpose of this is study is to assess the efficacy of pre-operative intravitreal bevacizumab (IVB) (Genentech, South San Francisco CA) in improving visual acuity, reducing operative time, complications, intra-operative and post-operative hemorrhage following small gauge pars plana vitrectomy (PPV) (23-gauge, 25-gauge or 27-gauge ) compared to small gauge PPV (23-gauge, 25-gauge or 27-gauge) alone in eyes with tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy (PDR). Hypothesis: Preoperative IVB may be beneficial for membrane dissection in diabetic tractional retinal detachment with minimally invasive vitreoretinal surgery (23-gauge transconjunctival sutureless vitrectomy \[TSV\]). In addition, post-operative rebleeding may be decreased.

This will be a prospective, randomized, active-controlled study of 224 eyes of patients with the diagnosis of TRD secondary to PDR. Participants will be screened for eligibility. Eligible patients will be examined at baseline to determine their ocular condition and randomized into 2 arms. Patients will be randomized in a 1:1 ratio to the study arm.

1. Control arm: PPV without pre-operative bevacizumab (Sham injection).
2. Study arm: Pre-operative bevacizumab (3-5 days) before PPV.

In the study arm, an intravitreal bevacizumab injection at a dose of 1.25 µg/0.05 mL will be scheduled 3 to 5 days before minimally invasive vitreoretinal surgery (MIVS).

The purpose of the current study is to determine the effectiveness and safety of an intravitreal injection of 1.25 mg of bevacizumab as a pre-operative adjunct to PPV in eyes with TRD secondary to PDR.

Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy

Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy: Results of the Pan-American Collaborative Retina Study (PACORES) Group

We would now like to examine molecules in the vitreous humor and epiretinal membranes to gain insight and better assess the efficacy and outcomes of pre-operative intravitreal bevacizumab.

Early (\<1 month) and late (≥ 1 month) post-operative vitreous hemorrhage (VH) (Yes or No)

Mean change in best-corrected visual acuity (BCVA) at 12 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Group-Matched Study With Belzupacap Sarotalocan (Bel-sar; AU-011) or Plaque Radiotherapy for Primary Indeterminate Lesions or Choroidal Melanoma (IL/ CM)	NCT05266430	Choroidal Melan... Indeterminate L...	Standard of Car... AU-011	18 Years -	Aura Biosciences
Clinical Study of Structural and Functional Evaluation of the Visual Pathway	NCT03591315	Pituitary Adeno... Visual Impairme... Sellar Tumor Neuroimaging	resting state f... visual tasking ... diffusion tenso... automated visua... visual acuity	18 Years - 60 Years	Xiangya Hospital of Central South University
Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy	NCT01976923	Tractional Reti...	Intravitreal be... Small-gauge par...	18 Years -	King Khaled Eye Specialist Hospital

Spots Global Cancer Trial Database for visual acuity