Rare Diseases

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Lethal Congenital Contracture Syndrome 2

All Drugs and Chemicals

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Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitogens

In Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.

GSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.

GSK2849330

89Zr-GSK2849330 solution for intravenous administration diluted with GSK2849330 Solution for Infusion (unlabelled GSK2849330) with a target radioactivity of 37MBq and a total antibody concentration of 0.4 mg/mL or 1.2 mg/mL.

89Zr-GSK2849330

GSK Clinical Trials

Human epidermal growth factor receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody (mAb) targeting HER3, is a new agent for subjects whose tumors express HER3. This study aims to characterise the biodistribution and dose-receptor occupancy relationship of GSK2849330 in patients with advanced HER3 expressing solid tumours via the use of PET imaging. This study will be conducted in two parts. Part 1 will be the imaging phase where each subject will receive two doses of GSK2849330 containing both Zirconium-89 (89Zr) labelled GSK2849330 and unlabeled GSK2849330. The amount of unlabeled GSK2849330 present in each dose will be varied to explore the effect on target mediated uptake of 89Zr into HER3 expressing tissues and tumors. Subjects will then proceed to the continuation phase (Part 2) for continued treatment with unlabelled GSK2849330. The study is planned to enroll approximately 12-15 subjects.

Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors

An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium to Investigate the Biodistribution of Anti-HER3 Monoclonal Antibody (mAb) GSK2849330 and Characterize Its Dose-receptor Occupancy Relationship in Subjects With Advanced HER3-Positive Solid Tumors

IPD for this study will be made available via the Clinical Study Data Request site.

Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.

RoIs will be outlined to represent whole organs and include the volumes encircled

Anatomical localization of radiolabel will be evaluated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Uptake of GSK2849330 in tumors will be estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Change in uptake parameters following dose 1 and 2 will estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Average radioactivity concentration will be determined and expressed as SUV and is equal to tissue radioactivity concentration normalized by administered amount of radioactivity per body weight.

Features of tumor will include central necrosis, irregular shape, non-uniform uptake and lesion ID

Measurements will include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC(0-t), AUC(0-Tau) (repeat dosing) and/or AUC(0-Infinity) (single dose), apparent terminal phase elimination rate constant (lambda z) and apparent terminal phase half-life (t½)

AEs and SAEs will be collected from the time the first dose of study treatment is administered until 45 days following discontinuation of study treatment

Clinical laboratory tests will include clinical chemistry, routine urinalysis, haematology laboratory evaluations and additional parameters

LVEF will be assessed as a measure of safety and tolerability measured by echocardiography (ECHO) or multi gated acquisition (MUGA) scans

Vital sign measurements will include systolic and diastolic blood pressure (BP), temperature, and pulse rate

Samples will be analyzed for the presence of anti-GSK2849330 antibodies using a validated immunoelectrochemiluminescent (ECL) assay.

GlaxoSmithKline

Neoplasms

Symptoms and General Pathology

Glioblastoma

Hypoxia

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

pretherapy(\[18F\]-FMISO) positon emission tomography-computed tomography. Different acquisition protocols will be tested and a wild panel of quantification parameters issued from published studies and original ones developed by our team enable to describe \[18F\]-FMISO uptake will be used.

18F]-FMISO PET-CT

Aymeri HUCHET, PHU

Hypoxia is recognized to be an independent predictor of clinical outcome in oncology. PET using \[18F\]-FMISO has been described to be useful for the non invasive assessment of hypoxia in cancer. The use of this radiotracer for brain tumours is very limited and there is no standard to acquire and quantify \[18F\]-FMISO uptake. So there is a need for a methodological evaluation of this PET tracer The purpose of this research is to define optimal parameters for acquisition and data exploitation to quantify \[18F\]-FMISO uptake and so predict clinical outcome in glioblastomas.

Low sensitivity to radiation of glioblastoma is partly caused by hypoxia. Hypoxia in tumours is not predicted by tumour size. Detecting and monitoring tissue oxygenation are of great interest to modify therapeutic strategies, including local dose escalation for radiotherapy or select chemotherapeutic agents with better impact in glioblastomas.

PET with appropriate radiotracers, especially \[18F\]-FMISO, enables non-invasive assessment of hypoxia. \[18F\]-FMISO only accumulates in viable hypoxic cells. So, it has been demonstrated that PET using 18F-FMISO is suitable to localize and quantify hypoxia. But there isn't any optimal acquisition protocol or standardized images quantification treatment. Thus, the interpretation of \[18F\]-FMISO PET images and the predictive value of \[18F\]-FMISO SUV (Standardized Uptake Value) remain unclear explaining the need of methodological approaches.

Hypoxia is one of the worst prognostic factors of clinical outcome in glioblastomas. Today, it is well admitted that hypoxia is heterogeneous, variable within different tumour types and varied spatially and temporally. Hypoxia induced proteomic and gene expression changes that lead to increase angiogenesis, invasion and metastasis. So the hypoxic fraction in solid tumours reduces their sensitivity to conventional treatment modalities, modulating therapeutic response to ionizing radiation or certain chemotherapeutic agents. This is particularly important in glioblastomas. Hypoxic cells in solid tumours could influence local failure following radiotherapy and has been associated with malignant progression, loco regional spread and distant metastases and represents an increasing probability of recurrence.

Thus, the non-invasive determination and monitoring of the oxygenation status of tumours is of importance to classify patients' outcome and modify therapeutic strategies in those tumours. Actually the oxygenation status of individual tumours is not assessed routinely. Numerous different approaches have been used to identify hypoxia in tumours. Eppendorf oxygen probe measurements (pO2 histography) may be considered as a 'gold standard' for hypoxia in human malignancies. However, it is an invasive method being confined to superficial, well accessible tumours and requires many measures. PET using \[18F\]Fluoro-deoxyglucose (\[18F\]-FDG), allows non-invasive imaging of glucose metabolism and takes a growing place in cancer staging, but \[18F\]-FDG can't assess correctly the oxygenation status of tumours and is not suitable for brain tumor. PET with appropriate radiotracers enables non-invasive assessment of presence and distribution of hypoxia in tumours. Nitroimidazoles are a class of electron affinic molecules that were shown to accumulate in hypoxic cells in cultures and in vivo. \[18F\]-FMISO is the most frequently employed tracer; its intracellular retention is dependent on oxygen concentration. Consequently \[18F\]-FMISO has been used as a non-invasive technique for detection of hypoxia in human. Different authors have demonstrated that it is suitable to localize and quantify hypoxia. Thus, \[18F\]-FMISO PET has been studied to evaluate prognosis and predict treatment response. However, some investigators report an unclear correlation between Eppendorf measurements and standardized uptake values (SUV). This observation may be explained by the structural complexity of hypoxic tumour tissues. Nevertheless, there is a need of standardized procedures to acquire and quantify \[18F\]-FMISO uptake. Actually the use of this tracer is very limited in clinic and the academic studies have included small populations of patients and suffer of the heterogeneity of technical procedures.

The aim of this study is to determine the optimal acquisition protocol and treatment parameters enable to describe \[18F\]-FMISO uptake in glioblastomas known to be hardly influenced by hypoxia. Then, validate \[18F\]-FMISO-PET as a prognostic maker of recurrence.

We will introduce a pretherapy \[18F\]-FMISO PET-CT in the treatment planning of patients suffering of different newly diagnosed glioblastoma and eligible to a radical treatment with curative intent, consisting of conformational radiotherapy and chemotherapy. \[18F\]-FMISO PET-CT results will not be take into account for the patient management. We will test different acquisition protocols and use a wild panel of quantification parameters issued from published studies and original ones developed by our team enable to describe \[18F\]-FMISO uptake. Patients will be followed clinically and para-clinically during one year after the end of the treatment according to the edited recommendations of each tumour type and grade to analyze outcome (failure is define as persistent disease in the primary site, progression of disease, locoregional relapse after complete response or distant metastasis). Thus we will be able to measure failure free survival and determine overall survival.

Evaluation of [18F]-FMISO for Non Operated Glioblastoma

Methodological Evaluation of Fluor 18 Labelled Fluoromisonidazole ([18F]-FMISO) Positon Emission Tomography-Computed Tomography (PET-CT) for Non Operated Glioblastoma

University Hospital, Bordeaux

Neoplasm Metastasis

Antineoplastic Agents

Bevacizumab

Angiogenesis Inhibitors

Fosbretabulin

Combretastatin

Antineoplastic Agents, Immunological

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

Combretastatin A4 Phosphate (CA4P)

Bevacizumab (Avastin)

Paul Nathan, MD

Hillori Connors, MS

Peter Harris, MD

The purpose of this study is to determine the safety and tolerability of three dose levels of combretastatin A4 phosphate (CA4P) given intravenously (IV) in combination with bevacizumab every 14 days in patients with advanced solid tumors. The maximum tolerated dose will be defined if it is at one of the three dose levels under study.

Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors

OXC4P1-105: A Phase I Study of the Safety, Tolerability, and Antitumor Activity of Escalating Doses of Combretastatin A4 Phosphate Given in Combination With Bevacizumab to Subjects With Advanced Solid Tumors

Mateon Therapeutics

Skin and Connective Tissue Diseases

Breast Neoplasms

Use of REIMS iKnife in breast conserving surgery

REIMS iKnife

Daniel Leff

Zoltan Takats

REI-EXCISE is a multicentre, prospective, non-randomised feasibility study, aimed to evaluate the diagnostic accuracy of rapid ionisation mass spectroscopy using an iKnife device. The iKnife will collect vapour, a by-product of surgery, which will pass through the mass spectrometer machine for analysis in order to evaluate what is "normal" and what is "cancerous" breast tissue.

There is an urgent need to address high rates of close or positive margins and re-operative breast cancer surgery, which commonly results from the inability of the surgeon to rapidly and reliably evaluate resection margin status intra-operatively.

This study therefore seeks to address this problem by aiming to develop a method for near real time, in vivo intra-operative tissue classification that may be used by breast surgeons as an intelligent knife (or "iKnife") to better guide oncological margin control. The method known as Rapid Evaporative Ionisation Mass Spectrometry (REIMS) technology uses mass spectrometric and chemometric analysis of the tissue specific ionic content of the surgical diathermy smoke plume for the rapid identification of dissected breast tissues.

There are no additional treatment interventions as part of REI-EXCISE. The main study procedures are breast conserving surgery using the REIMS iKnife for mass spectral analysis of each surgical margin and correlation between the results of a software recognition algorithm that capitalised on the spectral data (i.e. iKnife margin = positive / negative) with conventional histopathological assessment. False positive iKnife data will be further interrogated with digital droplet polymerase chain reaction and imprint cytology assessment.

Resected tissue samples will undergo detailed histopathological examination using a standard reporting schema based on the Royal College of Pathologists guidelines for breast specimen processing and the results of the histological examination of the tissue along the electrosurgical dissection line will be compared to the results of mass spectrometric tissue identification.

Real Time Tissue Characterisation Using Mass Spectrometry REI-EXCISE iKnife Study

Rapid Evaporative Ionisation Mass Spectrometry for Examination of Circumferential Surgical Excision Margins

Final versions of the anonymised databases and data files will be made available to the wider research community including other groups interested in breast cancer margin technologies and clinical applications / translation of mass spectroscopy.

Imperial College London retains copyright of the databases and data files. As part of the registration process users must agree to the conditions in the Data User Agreement including: restrictions against attempting to identify participants; destruction of data after analysis; reporting responsibilities (i.e. any publication arising as a result of sharing of the data will need to acknowledge the project PIs: Zoltan Takats \& Daniel Leff and Cancer Research United Kingdom as the funder); respecting the embargo period regarding publication; proper acknowledgment of the data resource and restrictions on sharing with third parties. A Data User Agreement must be signed before access to the data is permitted.

The diagnostic accuracy of rapid ionisation mass spectroscopy for oncological margin status will be measured during breast conserving surgery (BCS) (n=35 patients with positive margins). The primary end-point will allow to report accuracy (sensitivity and specify) of rapid ionisation mass spectroscopy to distinguish between patients with at least one close or positive margin and those without close or positive margin.

This study will quantify whether REIMS adds significantly to the intra-operative time taken to perform breast conserving surgery. Thus, the data generated with REI-EXCISE trial will report the difference in specimen excision time using iKnife as compared to conventional electrosurgery.

This study will be collecting data to understand if end-users are sufficiently satisfied with REIMS technology framework (including modified hand-piece) , and are willing to use it routinely during breast conserving surgery (BCS). This will be conveyed by analysing the end user questionnaire completed by the surgeons to infer if they are satisfied with the use of REIMS instrumentation in vivo to perform BCS.

The intra-operative REIMS analysis will be used to accurately predict/measure the oncological status of the surface of the wide local excision cavity. The data will be reported as the proportion of patients with all close or positive margins correctly detected as positive by iKnife and as the proportion of patients with no margin malignancy correctly detected by iKnife among the true negative patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors	NCT02345174	Cancer Neoplasms	GSK2849330 89Zr-GSK2849330	18 Years -	GlaxoSmithKline
Evaluation of [18F]-FMISO for Non Operated Glioblastoma	NCT00906893	Glioblastoma	18F]-FMISO PET-...	18 Years -	University Hospital, Bordeaux
Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors	NCT00395434	Tumors	Combretastatin ... Bevacizumab (Av...	18 Years -	Mateon Therapeutics
Evaluation of [18F]-FMISO for Non Operated Glioblastoma	NCT00906893	Glioblastoma	18F]-FMISO PET-...	18 Years -	University Hospital, Bordeaux
Real Time Tissue Characterisation Using Mass Spectrometry REI-EXCISE iKnife Study	NCT03432429	Breast Cancer Surgery	REIMS iKnife	18 Years -	Imperial College London
Real Time Tissue Characterisation Using Mass Spectrometry REI-EXCISE iKnife Study	NCT03432429	Breast Cancer Surgery	REIMS iKnife	18 Years -	Imperial College London

Spots Global Cancer Trial Database for tumours

Every month we try and update this database with for tumours cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tumours

Every month we try and update this database with for tumours cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tumours cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.