Neoplasms

All Conditions

Rare Diseases

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Dermatologic Agents

All Drugs and Chemicals

Aminolevulinic Acid

Surgery to resect the GB using Diffusion Tensor Imaging (DTI) and intraoperative Ultrasound (iUS) (navigated iUS where available) in addition to standard care (i.e. neuronavigation based on preoperative MRI and intraoperative use of 5-aminolevulinic acid (5-ALA))

The comparator is standard care as per current NICE guidelines (i.e. neuronavigation based on preoperative MRI and intraoperative use of 5-ALA).

Standard of Care

Additional DTI scan during routine pre-operative tumour MRI scan, additional use of intraoperative ultrasound in addition to normal to standard of care (Neuronavigation and intraoperative 5-ALA)

Additional pre- and intra-operative imaging

Amy Taylor

Colin Watts

Giles Critchley

Neil Barua

Stephen Price

George Eralil

Sandeep Solanki

Anna Solth

Paul Brennan

Chittoor Rajaraman

Robert Corns

Michael Jenkinson

Edward McKintosh

Keyoumars Ashkan

Sophie Camp

Dipankar Nandi

Anil Varma

Damian Holliman

Stuart Smith

Puneet Plaha

James Palmer

Isaac Phang

Nik Haliasos

Yahia Al-Tamimi

Paul Grundy

Erminia Albanese

Functional and ultrasound-guided resection of glioblastoma: assessing the use of additional imaging during surgery to improve outcomes for patients with glioblastoma brain tumours

Stage 1 (IDEAL IIB study) of the trial is observational only and all participants will receive all technologies during surgery.

Stage 2 will be randomised. Randomisation will be via the web-based service provided by the Oxford Clinical Trials Research Unit (OCTRU), using the method of minimisation. Participants will be randomised 1:1 to either:

1. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA)(Control arm)
2. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA) AND of DTI neuronavigation and NiUS (Intervention arm)

At baseline all participants will undergo a routine preoperative neuronavigation MRI scan. Those participants randomised to the experimental arm, will also have a DTI scan (additional 5 minutes in the MRI). All participants will then undergo the planned resection of their tumour, with the additional technologies if they are in the experimental arm. Following surgery, participants in both arms have the same follow up schedule and undergo standard clinical care for a total of 24 months.

FUTURE-GB is a 2-Stage trial: Stage 1 is a non-randomised multicentre learning and evaluation Stage (IDEAL IIB study), and Stage 2 a prospective, multicentre definitive randomised controlled trial.

Functional and Ultrasound Guided Resection of Glioblastoma

FUTURE-GB Trial (Functional and Ultrasound-guided Resection of Glioblastoma) A 2-Stage Trial. A Learning Phase Evaluation of Participating Centres, Followed by a Randomised, Controlled Multicentre Phase III Trial.

To assess the sensitivity and specificity of the anatomico-spatial location of DTI fibre tracts compared with intraoperative direct electrical stimulation/behavioural change without stimulation but related to adjacent white fibre tract in patients undergoing awake surgery, or motor evoked potential changes in patients undergoing surgery.

Measured by sensitivity and specificity calculation using pre and post-surgery MRI images

To assess the sensitivity and specificity of iUS\* to identify the tumour boundary when compared with 5-ALA, navigated biopsies will be taken from tumour boundary tissue planned for resection.

Intra operative iUS\* images and post-operative MRI scans and Intraoperative biopsy samples

Sites are qualitatively assessed through a standardisation stage, providing feedback to enable learning and ensure the workflow is followed. Sites with satisfactory data will "progress" and pass into Stage 2.

The measures assessed in combination are:

1. Operation length, in normal range for this surgery.
2. Use of DTI neuronavigation \& iUS to achieve maximal safe tumour resection without major neurological deficit, measured by getting clear, relevant images for the DTI \& US scans, and accurate pre-operative tractography.
3. Extent of tumour resection (cm³ remaining) on postoperative MRI scan.
4. Surgical Complications/Serious Adverse Events-measured from recorded post-operative complications and a 6-month notes check to ensure patient safety.

If the assessment panel is satisfied with the data after \~3 recruits, a site will progress into Stage 2 of the trial, the RCT. Data will be analysed for Stage 1 once all sites have progressed through into Stage 2 of the trial.

This is measured by a composite of:

1. Change in global health status domain of the QLQ-C30 questionnaire (Quality of Life Questionnaire Cancer) from baseline to final questionnaire completion. Questionnaires are administered at baseline, 6 weeks, then every 3 months until 24months.
2. Progression Free Survival (PFS). This is measured by radiological tumour progression on imaging, which is taken 3-months post-op and 3-monthly thereafter.
3. Overall Survival (OS) with an event defined as either deterioration, progression or death.

This is measured using a combination of specific questions (physical functioning and social functioning) in the QLQ-C30 (Quality of Life Questionnaire Cancer) and BN20 questionnaire (Quality of Life Questionnaire Brain) (motor dysfunction and communication deficit questions), combined with the values of Progression Free Survival (PFS) and overall survival (OS) taken from the primary outcome.

Questionnaires are administered at baseline, 6 weeks, then every 3 months until 24months.

Defined similar to DFS with the exception that progression is excluded as an event (i.e. only deterioration or death are considered). There will be five time to deterioration outcomes, one for each of the domains utilised in the primary and secondary DFS outcomes, used in turn to define deterioration

OS (time from randomisation to death or trial closure)

PFS (time from randomisation to radiological tumour progression on imaging, as agreed in local MDT

This involves using the post-operative MRI scan as a reference point and making comparisons will the ensuing MRI reports that are recieved 3 months post-surgery and 3 monthly thereafter until 24 months post-surgery.

Extent of resection as percent of pre-operative tumour volume on postoperative contrast enhanced MRI

Number and type of surgical complications

Number of patients eligible for adjuvant treatment

Measured by any change in the functional performance assessment which consistes of a combination of:

1. The WHO (World Health Organisation) performance status
2. A 5-minute telephone mini-MoCA (The Montreal Cognitive Assessment, Montreal Version)
3. Barthel Index
4. MRC (Medical Research Council) grading of power in all 4 limbs

Assessments are made at baseline, at hospital discharge, 6 weeks post-op, 3 months post-op, then 3 monthly thereafter until 24 months.

Assessed using comparisons between the patient and proxy responses to the Quality of Life questionnaires administered. Specifically comparisons between the answers to questions 29 and 30 of the QLQ-C30.

Imperial College Healthcare NHS Trust

Efficacy and Mechanism Evaluation (EME) Programme

University of Oxford

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Participants in this study arm will still receive Optune array layout mapping based on standard MR imaging sequences.

Participants in this study arm will receive Optune array layout mapping created from advanced MR imaging sequences obtained through trial enrollment.

All study participants will receive whole brain spectroscopy imaging as a part of MRI study time points. Participants assigned to the advanced MR imaging array mapping layout study arm will receive tumor treating fields mapping from Optune that is created from the spectroscopy sequences or advanced MR imaging. Participants assigned to the conventional array mapping layout will still receive advanced imaging sequences or spectroscopy imaging at all time points.

Whole Brain Spectroscopy Imaging Array Mapping Layout

Demetrius Lee

Neuroradiology Research Core

Kristina Vineis

Suyash Mohan, MD

Sanjeev Chawla, PhD

Suyash Mohan, MD, PDCC

This research study is for Glioblastoma (GBM) patients who will be beginning Optune as part of their clinical care, which is a novel treatment that utilizes - tumor treating fields (TTFields), (aka, electrical therapy), which has shown to improve overall survival in large multi-center trials. As a part of this study, participants will either receive Optune with "standard array mapping" (based on regular contrast enhanced MRI) or an "alternative (more precise) array mapping" based on sophisticated state of the art MRI techniques including "whole brain spectroscopy". Whole brain MRI spectroscopy provides additional metabolic information to map out the full extent of tumor spreading within the brain (far beyond from what is seen on regular MRI), by identifying certain metabolites that are present in cancer cells versus healthy tissue. This study is being performed to show whether alternative array mapping improves treatment outcomes, as opposed to the standard array mapping, by maximizing delivery of TTFields dose, thereby achieving more effective tumor cell killing, decreasing the rate of local recurrence, and improving the overall survival as well as quality of life measures.

WBSI Guided Personalized Delivery of TTFields

Whole-Brain Spectroscopy Guided Personalized Mapping of Transducer Arrays for Glioblastoma Patients Receiving Tumor Treating Fields

Using whole brain spectroscopy imaging, diffusion and perfusion MR imaging, a combined multiparametric approach will be utilized to compare treatment response from patients enrolled in two study arms.

Time until local recurrence and overall survival status will be calculated in months

NovoCure Ltd.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Abramson Cancer Center at Penn Medicine

Behaviors and Mental Disorders

Aggression

Patients affected by brain tumors undergoing surgical resection; hypomethylation or hypermethylation of MGMT assessed post-surgery for patients affected by GBM; adult patients (≥18 years), both sexes; Patients undergoing Stupp protocol including patients aged \> 70 years performing the hypofractionated protocol and three weeks of chemotherapy; Karnofsky Performance Status (KPS)\> 60 assessed post-surgery; freely given written informed consent prior to any activity related to the study.

cellular and molecular analysis on cancer stem cells and endothelial cells from tumor biopsies and investigation of tissue and systemic biomarkers

cell isolation from tumor biopsies and biomarker investigation

Stefania E Navone, PhD

Giovanni Marfia, MD, PhD

Stefania Navone, PhD

Laura Guarnaccia, PhD

Laura Begani, MSc

Marco Locatelli, Md, PhD

Claudia Fanizzi, MD

Luigi Schisano, MD

Antonella Ampollini, MD

Manuela Caroli, MD

Giulio Bertani, MD

Giorgio Fiore, MD

Antonio D Ammando, MD

Elena Scagliotti, MSc

Giorgia Abete Fornara, MSc

Marco Locatelli, MD, PhD

Tumors of the central nervous system affect 21 people per 100,000 every year, a figure that refers to countries with advanced economies, with an increase in incidence over time. Experimental evidence suggests that cancer stem cells (CSCs) may play a key role in the malignancy of these tumors. In fact, due to the hypoxic tumor microenvironment, these cells are able to create compensatory pathways that confer stem-like, angiogenic and pro-tumoral functions. Furthermore, it has been demonstrated that brain tumor stem cells are radio- and chemo-resistant and therefore not treatable with the therapeutic protocols currently in use. To date, in fact, there are no definitive treatments for the eradication of brain tumors. In this scenario, sphingolips, a class of lipid deputized to several physiological functions, are also involved in tumor onset, progression, drug resistance, and aggressiveness. In hypoxic tumor microenvironment, CSCs present a modified rheostat in the metabolism of sphingolipid, in favor of Sphingosine-1-phosphate (S1P).

S1P is an intermediate of sphingolipid metabolism, formed from sphingosine through the action of sphingosine kinases (SK). Increasing evidence suggests that S1P acts as a tumor-promoting signal, predominantly in the extracellular environment, regulating important cellular properties correlated with tumor potential.

The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment.

Tumors of the central nervous system affect 21 people per 100,000 every year, a figure that refers to countries with advanced economies, with an increase in incidence over time. Among tumors of the central nervous system, Glioblastoma (GBM) is the most frequent and aggressive malignant tumor with an average life expectancy of approximately 12 months and a survival of less than 5% in the following 5 years to the diagnosis. The growth and progression of GBM are dependent on a specialized subpopulation of tumor cells called "cancer stem cells" (CSCs). CSCs are chemo- and radio-resistant, are responsible for relapses and therefore should constitute an important target of therapeutic strategies, but the mechanisms underlying their biology are still poorly understood. Hypoxia, through the hypoxia-inducible factor (HIF) and sphingolipid pathway, plays a key role in the control of tumor growth and angiogenesis and represents, perhaps, the most effective adaptation mechanism of the tumor itself. Indeed, The hypoxic microenvironment of solid tumors gives them greater aggressiveness, an increase in the expression of proteins linked to angiogenesis, anaerobic energy metabolism and adaptation to oxidative stress which facilitates the onset and proliferation of CSCs.

This study supports the evidence that the hypoxic microenvironment regulates the state of CSCs, and therefore influencing the response to the current pharmacological treatments.

Although S1P can act as an intracellular second messenger, most of its effects are exerted as an extracellular mediator, through binding to specific G protein-coupled receptors, originally known as EDGs and now called S1P receptors (S1PRs). Our group has previously demonstrated that acquired modifications in the metabolism of sphingolipids, in particular in the regulation of S1P, are able to confer stem-like and chemo-resistance properties to CSCs in patients with GBM.

The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment.

Through the study of sphingolipid metabolism, new markers and inhibitors will be identified to be delivered to inhibit CSC proliferation and tumor progression.

With this approach the investigators will be able to evaluate how the tumor microenvironment and the molecular and metabolic characteristics of the tumor influence cellular communication and whether this process can be influenced by new pharmacological treatments. This study could highlight new pathways and tumor-specific alterations to stratify new therapeutic strategies and to identify new potential biomarkers in diagnosis and monitoring, thus improving the prognosis of patients suffering from brain tumors.

cells from tumor biospsies and blood circulation

Development of Therapeutic Approaches Modulating Molecular Targets Implicated on Cancer Stem Cell-related Aggressiveness

Strategies for the Development of Multimodal Therapies in Tumors of the Central Nervous System: Identification of New Molecular and Metabolic Targets Implicated in Survival and Chemoresistance Involving Endothelial and Cancer Stem Cells

Evaluation of prognostic and predictive role of molecular and metabolic markers of the tumor. Determination of gene and protein expression of a panel of markers related to stemness, angiogenesis/hypoxia, and sphingolipid signaling.

Identification of new tissue and circulating biomarkers with predictive and prognostic significance

Investigation of cellular response following new treatments determined by molecular and metabolic specific signature; determination of a panel of markers differently expressed following pharmacological treatments; evaluation of the prognostic and predictive role of tumor marker expression

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Symptoms and General Pathology

Disease Progression

Pharmaceutical Solutions

Fluorides

Radiopharmaceuticals

Axumin is a positron emitting radiopharmaceutical that has been studied in vivo in humans in a number of tumor types with positron emission tomography (PET/CT). 18F-Fluciclovine is a fluorine-18 labeled synthetic amino acid analog that is FDA approved as a PET imaging agent for prostate cancer recurrence, however, it has also been tested in other tumors. Investigators will use a typical dose of 18F-fluciclovine that is used for clinical studies in glioblastoma. This will be 5 mCi (approximate range for most studies is anticipated to be 5 mCi +/- 20%), but a lesser dose may be injected if, in the opinion of a Nuclear Medicine Authorized User, complete imaging data could be generated.

To compare 18F-fluciclovine PET uptake measures in glioblastoma patients with tumor progression versus pseudoprogression

Axumin, Intravenous Solution

Subjects with histologically proven glioblastoma (GBM) who are suspected to have progression and are candidates for a surgical resection according to standard of care may be eligible for this study. Subjects may participate in this study if they are at least 18 years of age.

Positron emission tomography (PET/CT) imaging will be used to evaluate fluciclovine uptake at sites of suspected progression before planned surgery. In addition, clinical brain MRI with and without contrast will be used to evaluate the tumor pre-operatively. This is a non-therapeutic trial in that imaging will not be used to direct treatment decisions.

Investigators anticipate enrolling up to 30 subjects who will undergo a clinical brain MRI examination with and without contrast and a research 18F-Fluciclovine PET/CT scan of the brain prior to surgery. They will also have a blood draw preoperatively to collect samples for cfDNA analysis. PET/CT imaging sessions will include an injection of approximately 5 mCi (range for most studies is anticipated to be 5 mCi +/- 20%) of 18F-Fluciclovine.

This is a pilot study in subjects with a histologically proven diagnosis of glioblastoma (GB) who have completed chemoradiation and now have new contrast enhancing lesions or lesions showing increased enhancement ( 25% increase) who are recommended for a clinical surgical resection. Subjects may participate in this study if they are at least 18 years of age, most participants will be receiving care at the clinical practices of the University of Pennsylvania. Subjects who come to the University of Pennsylvania for diagnosis and/or treatment of GB and who meet the study inclusion criteria may be approached by study personnel for recruitment into this study. Subjects will be approached about study participation regardless of race or ethnic background. Investigators anticipate enrolling up to 30 participants. Subjects who consent but do not complete the study imaging will be considered not evaluable and will be replaced. Accrual will likely occur over approximately 1-2 years. After undergoing screening assessments and verifying eligibility for study participation subjects will undergo a research 18FFluciclovine PET/CT scan of the brain and a clinical brain MRI with and without gadolinium contrast, all baseline imaging will be done prior to (within 1 week) of the surgical procedure. The PET-CT and MRI can be performed in any order.

To compare 18F-fluciclovine PET uptake measures in glioblastoma patients with tumor progression vs pseudoprogression. To determine a multidimensional signature using 18F-fluciclovine PET, MRI, and plasma cfDNA that accurately differentiates tumor progression from pseudoprogression in post-chemoradiation GBM.

[18F]Fluciclovine in Post-treatment Glioblastoma ( Axumin )

Multimodality 18F-Fluciclovine PET, MRI and Cell Free Circulating DNA to Differentiate Tumor Progression From Pseudoprogression in Patients With Glioblastoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Functional and Ultrasound Guided Resection of Glioblastoma	NCT05399524	Glioma Glioblas...	Standard of Car... Additional pre-...	18 Years - 70 Years	University of Oxford
WBSI Guided Personalized Delivery of TTFields	NCT05086497	GBM Glioma Glioblas... Tumor, Brain	Whole Brain Spe...	22 Years -	Abramson Cancer Center at Penn Medicine
Functional and Ultrasound Guided Resection of Glioblastoma	NCT05399524	Glioma Glioblas...	Standard of Car... Additional pre-...	18 Years - 70 Years	University of Oxford
Development of Therapeutic Approaches Modulating Molecular Targets Implicated on Cancer Stem Cell-related Aggressiveness	NCT06348693	Glioblastoma Glioma Glioma Glioblas...	cell isolation ...	18 Years -	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
[18F]Fluciclovine in Post-treatment Glioblastoma ( Axumin )	NCT03990285	Glioma Glioblas...	Axumin, Intrave...	18 Years -	Abramson Cancer Center at Penn Medicine

Spots Global Cancer Trial Database for glioma glioblastoma multiforme