Neoplasms

All Conditions

Rare Diseases

Glioblastoma

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

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Patients who suffer from a suspected GBM and will undergo a microsurgical procedure for diagnosis verification. MRI and Positron Emission Tomography (PET) scans are scheduled prior to microsurgery, post microsurgery and after having completed radiochemotherapy and an additional scan after TMZ chemotherapy.

Patients enrolled in Group B suffer from a suspected GBM which cannot be accessed microsurgically either due to a an eloquent location of the tumor, or patient's refusal to undergo surgery. In these patients, diagnosis will be obtained by means of stereotactic surgery. After an initial PET and MRI scan prior to biopsy, patients will be monitored by post radiochemotherapy as well as post 3-months chemotherapy MRI/PET scans.

Joerg C. Tonn, Prof. Dr.

The aim of this study is to establish FET-PET as an additional therapy assessment parameter in patients diagnosed with a glioblastoma multiforme receiving radiochemotherapy and adjuvant chemotherapy after previous resection or biopsy.

DNA and RNA samples for MGMT methylation and LOH 1p and 19q status analysis

Usefulness of Therapy Monitoring by Means of [(18)F]Fluoroethyltyrosine-Positron Emission Tomography (FET-PET) in Glioblastoma Multiforme Patients

Quantification of Therapy Effects After Microsurgery, Percutaneous Irradiation and Chemotherapy by FET-PET Analysis

Deutsche Krebshilfe e.V., Bonn (Germany)

Ludwig-Maximilians - University of Munich

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Intervention: iMRI-guided brain tumour biopsy. The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet imager will be used in all cases. After the patient's positioning, the preoperative reference examination is routinely carried out. The entry point, target and optimal biopsy trajectory are then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples are collected. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) is routinely performed to confirm and document the proper targeting and to exclude postoperative hyperacute intraparenchymal bleeding.

Intervention: Stereotactic frameless brain tumour biopsy. A frameless STx biopsy is performed for each patient from the control group with the use of a neuronavigation system. The entry point, target and optimal biopsy trajectory are defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).

The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet was used in all procedures.

iMRI-guided brain tumour biopsy

The entry point, target and optimal biopsy trajectory were defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).

Stereotactic frameless brain tumour biopsy

Wlodzimierz Jarmundowicz, Professor

Background: The aim of the study was to assess the safety and effectiveness of stereotactic brain tumour biopsy (STx biopsy) guided by low-field intraoperative MRI (iMRI) in comparison with its frameless classic analogue based on a prospective randomized trial.

Patients are prospectively randomized into a low-field iMRI group and a control group that undergo a frameless STx biopsy. The primary endpoints of the analysis are: postoperative complication rate and diagnostic yield, and the secondary endpoints: length of hospital stay and duration of operation.

INTRODUCTION Stereotactic brain biopsy (STx biopsy) offers a relatively straightforward, accurate and safe method of obtaining diagnostic tissue. Frameless computer-based neuronavigation is now widely used in brain tumor surgery. It has many advantages over frame-based techniques and provides similar accuracy to the rigid frame. One of the methods applied to improve diagnostic yield and safety is the usage of intraoperative magnetic resonance imaging (iMRI), proposed by Bernays et al. in 2002.

Besides the obvious indications given in previous papers, including STx biopsy of very small, deeply localized or cystic lesions, iMRI guidance is particularly useful in two cases. The first one is when a satisfactory 3D volume modality cannot be obtained during preoperative high-field diagnostic MR imaging. When using iMRI there is no need to perform preoperative 3D imaging of any kind and manually register the patient's head in a neuronavigation system before the operation, which helps to significantly improve the workflow. In our study the total amount of patients with insufficient neuroimaging - admitted from outside medical centers - is over 30%. The second case is for teaching purposes - frameless iMRI guided STx biopsy, is relatively uncomplicated and technically straightforward and can be introduced as the first procedure during training in neurosurgical intraoperative imaging.

Although the usefulness of ultra-low-field iMRI in STx biopsy was subsequently confirmed by other authors, according to our knowledge no previous published studies have compared iMRI to preoperative MRI for brain tumor biopsy according to evidence-based medicine guidelines (EBM). Though this method has been subject to slight criticism, it has been consequently applied in neurosurgical daily practice in recent years.

The aim of our study was to verify the safety and effectiveness of the STx biopsy guided by low-field iMRI in comparison with its frameless classic analogue basing on a prospective randomized parallel-group, controlled trial. In the current paper we present the study design and results of the interim analysis.

MATERIAL AND METHODS

Patients Patients who are - following contemporary recommendations - scheduled to undergo STx biopsy, are prospectively recruited for the study. Each patient sign a written consent to participate in the study.

Inclusion criteria The inclusion criteria were as follows: male and female patients ≥ 18 years with supratentorial brain tumor scheduled to undergo STx biopsy. The estimated number of patients needed to reveal the difference of over 5% between primary endpoints' - diagnostic yield and complications ratio - at the level of significance 0.05 and power 80% was 465 per each arm.

Exclusion criteria Patients unable to provide informed consent and those with metal implants which could prevent or influence the head MR study were excluded from the study.

Allocation Patients were prospectively allocated by minimization according to demographic (gender, age) and epidemiologic data (preoperative Eastern Cooperative Oncology Group Performance Status-ECOG- a scale providing information about neurological and social status of a patient with oncological disease, maximum tumor diameter, presence of contrast enhancement, independent risk factors of hemorrhage - basal and thalamic localization and preoperative diabetes) into the iMRI and the control group.

Intervention After being transferred to the operating room each patient was sedated with an intravenous infusion of Remifentanil with passive oxygen therapy and monitoring of vital functions. Additionally, the sites of head holder pins and skin incision were anaesthetized with 1% Lignocaine. All biopsies in both groups were performed via a 6 mm burr-hole with the use of the Vertec system (Medtronic Navigation, Louisville, CO, USA). A passively navigated side cut 2.2 mm biopsy needle was used. All operations were performed by one of the three first authors.

In the iMRI-guided group the head of each patient was immobilized with a 3-pin iMRI-compatible head holder. The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet was used in all procedures. Subsequently, after the patient's positioning, the preoperative reference examination was routinely carried out (T1+gadolinum, T2 or FLAIR weighted - depending on the pathology, axial 4 mm scans). Images were automatically transferred into the neuronavigation system (StealthStation, Medtronic Navigation, Louisville, CO, USA). The entry point, target and optimal biopsy trajectory were then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples (4 from the central and another 4 from the marginal part of the tumor) were collected according to the modified protocol described by Shooman et al., which made use of intraoperative histopathological examination obsolete. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) was routinely performed to confirm and document the proper targeting and - as proposed by Bernays et al. - to exclude postoperative hyperacute intraparenchymal bleeding.

A frameless STx biopsy was performed for each patient from the control group with the use of a neuronavigation system. The entry point, target and optimal biopsy trajectory were defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA). Following surgery the specimens were sent for independent histopathological analysis.

Postoperative care Postoperative care was conducted according to standard protocols and clinical guidelines. A postoperative follow-up head CT was subsequently performed 4 to 6 hours after each procedure. All patients were followed up with a clinical examination 2 weeks postoperatively performed by an independent and blinded for the allocation investigator.

Data collection Demographic and epidemiological data were collected prospectively. The primary endpoints were: the ratio of acute postoperative complications and the diagnostic yield. The presence of acute postoperative complication was noted if any of following findings was noted: (wound site infection up to two weeks after the operation, a new neurological deficit developed up to 24 hours following the operation and present in a follow up clinical examination 2 weeks postoperatively), intraparenchymal hematoma with radiological or clinical signs of the intracranial expansion.) and the diagnostic yield. The diagnostic yield was expressed according to the literature as a percentage of patients in whom the histopathological diagnosis was possible on the basis of the biological material obtained during the operation. Secondary endpoints included: the preoperative (LOSpre), postoperative (LOSpost) and total length of hospital stay (LOS) as well as the preparation (Tprep), operation (Top) and total operating room (TOR) time. The LOS and T were routinely measured and recorded in the central hospital files by the independent staff.

Intraoperative MRI-guidance in Frameless Stereotactic Biopsies

The Safety and Effectiveness of Low Field Intraoperative MRI-guidance in Frameless Stereotactic Biopsies of Brain Tumours - a Prospective Randomized Trial

The presence of acute postoperative complication is noted if any of following findings is present: wound site infection up to two weeks after the operation, a new neurological deficit developed up to 24 hours following the operation and present in a follow up clinical examination 2 weeks postoperatively, intraparenchymal hematoma with radiological or clinical signs of the intracranial expansion.

The diagnostic yield is expressed as the number of patients in whom the histopathological diagnosis was made based of the biological material obtained during the operation.

The preoperative (LOSpre), postoperative (LOSpost) and total length of hospital stay (LOS)

the preparation (Tprep), operation (Top) and total operating room (TOR) time

Wroclaw Medical University

M.D., Ph.D.

The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet is used in all procedures. Subsequently, after the patient's positioning, the preoperative reference examination is routinely carried out (T1+gadolinum, T2 or FLAIR weighted - depending on the pathology, axial 4 mm scans). The entry point, target and optimal biopsy trajectory are then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples (4 from the central and another 4 from the marginal part of the tumour) are collected. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) is routinely performed to confirm and document the proper targeting and to exclude postoperative hyperacute intraparenchymal bleeding.

Stereotactic intraoperative magnetic resonance (iMRI)-guided frameless brain tumour biopsy: The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a was used in all procedures.

iMRI

A frameless STx biopsy is performed for each patient from the control group with the use of a neuronavigation system. The entry point, target and optimal biopsy trajectory are defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).

Stereotactic frameless brain tumour biopsy: The entry point, target and optimal biopsy trajectory were defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).

Non-iMRI

The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet is used in all procedures. Subsequently, after the patient's positioning, the preoperative reference examination is routinely carried out (T1+gadolinum, T2 or FLAIR weighted - depending on the pathology, axial 4 mm scans). The entry point, target and optimal biopsy trajectory are then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples (4 from the central and another 4 from the marginal part of the tumour) are collected. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) is routinely performed to confirm and document the proper targeting and to exclude postoperative hyperacute intraparenchymal bleeding.

Stereotactic intraoperative magnetic resonance (iMRI)-guided frameless brain tumour biopsy: The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with was used in all procedures.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Poland

Region of Enrollment

The ECOG Scale of Performance Status:

0 - Fully active, able to carry on all pre-disease performance without restriction

1. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work
2. - Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. - Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. - Dead

ECOG Performance Status

Maximum tumour diameter

Enhancement noted

No enhancement noted

Number of participants with contrast-enhancing tumors.

Tumour enhancement

basal localisation of the tumor

non-basal localisation of the tumor

Number of participants with basal localisation of the tumor.

Basal localization

thalamic localisation of the tumor

extra-thalamic localisation of the tumor

Number of participants with thalamic localisation of the tumor.

Thalamic localization

Diabetes recorded

Diabetes not recorded

Number of participants with preoperative diabetes.

Diabetes

Dr. Marcin Czyz

Complications assessed: Haematoma, Neurological deterioration, Infection

Number of Participants Presenting With Complications

Diagnostic Yield

Length of the postoperative hospital stay

Total length of hospital stay

The length of preoperative hospital stay

The length of postoperative hospital stay

Length of Hospital Stay

Total OR time

Time of preparation

Time of the operation

Time

The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet is used in all procedures. Subsequently, after the patient's positioning, the preoperative reference examination is routinely carried out (T1+gadolinum, T2 or FLAIR weighted - depending on the pathology, axial 4 mm scans). The entry point, target and optimal biopsy trajectory are then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples (4 from the central and another 4 from the marginal part of the tumour) are collected. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) is routinely performed to confirm and document the proper targeting and to exclude postoperative hyperacute intraparenchymal bleeding.

Stereotactic intraoperative magnetic resonance (iMRI)-guided frameless brain tumour biopsy: The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) was used in all cases.

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

The Brevera Breast Biopsy System with CorLumina imaging technology is a vacuum-assisted biopsy device, which is used to remove breast tissue in a minimally invasive manner using stereotactic or tomosynthesis imaging.

Each of the participating sites will currently be using a vacuum assisted breast biopsy system along with a specimen radiography system (or other specimen imaging system).

A breast biopsy is a test that removes tissue or sometimes fluid from the suspicious area. The removed cells are examined under a microscope and further tested to check for the presence of breast cancer. A biopsy is a diagnostic procedure that can definitely determine if the suspicious area is cancerous.

Breast Biopsy

The Brevera Breast Biopsy System integrates tissue acquisition, real time imaging, and post biopsy handling all during the same procedure. This post-market clinical trial will be performed to obtain clinical/operational data and feedback on the Brevera Breast Biopsy System as compared to the current standard-of-care breast biopsy procedures

Only females (biologic) will be eligible for participation in the clinical trial.

A Post-Market Clinical Trial to Evaluate the Performance and Operation of the Brevera Breast Biopsy System

A Prospective, Block Stratified Clinical Trial to Evaluate the Performance and Operation of the Brevera Breast Biopsy System

The primary endpoint of this trial is the measured difference in procedure time between biopsies performed with the Brevera biopsy system with real time imaging and biopsies performed using the standard-of-care biopsy system at each clinical site.

Tissue weight and number of cores collected

Hologic, Inc.

Dermatologic Agents

Aminolevulinic Acid

Stereotactic biopsy will be performed on patients in the experimental group, who will then be discharged. If the histopathological diagnosis is not wildtype IDH non-mutated glioblastoma, the patient will be withdrawn from the study and receive conventional treatment. If wildtype IDH non-mutated glioblastoma is diagnosed, ten days after the biopsy, patients will undergo conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal, including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy, one session per day, five days a week, and concurrent temozolomide (TMZ) at 75 mg/m2/day for 7 days/week during the irradiation period (GEINO, 2016). Five weeks later, patients will undergo supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. Starting from 4 weeks post-surgery, TMZ will be administered for 6 months according to the Stupp protocol.

The Stupp protocol is a standard treatment regimen for glioblastoma, which involves a combination of radiotherapy and chemotherapy.

conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal, including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy, one session per day, five days a week, and concurrent temozolomide (TMZ) at 75 mg/m2/day for 7 days/week during the irradiation period

hypofractionated stereotactic radiotherapy

Stereotactic biopsy

supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring

resection

4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months

Chemotherapy

radiotherapy + TMZ concurrently after 4 weeks of resection surgery, as per usual protocol: Three-dimensional radiotherapy planning to deliver a total dose of 60 Gy, with a fractionation of 2 Gy/day, 5 days/week, encompassing a 1-2 cm margin around the contrast-enhancing region defined on T1 imaging or the entire abnormal volume defined on T2 or FLAIR imaging (Li et al., 2016) + TMZ at 75 mg/m2/day for 7 days/week, for 6 weeks during radiotherapy.

radiotherapy Stupp protocol

temozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.

Chemotherapy Stupp Protocol

Juan Antonio Barcia

Mª Rebeca Lliguin León

The goal of this clinical trial is to evaluate the safety and efficacy of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). The main questions it aims to answer are:

* What is the safety profile of neoadjuvant radiochemotherapy in terms of neurological deficit, radionecrosis, edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula?
* What is the efficacy of neoadjuvant radiochemotherapy in terms of progression-free survival, overall survival, cognitive function, and quality of life?

Participants will undergo the following tasks and treatments:

* Stereotactic biopsy and diagnosis confirmation.
* Conformal hypofractionated stereotactic radiotherapy with concurrent temozolomide.
* Supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring.
* Maintenance temozolomide administration for 6 months.

Researchers will compare the group receiving neoadjuvant radiochemotherapy to the control group following the standard Stupp protocol to assess safety and efficacy outcomes.

Objectives: To study the safety (primary) and efficacy (secondary) of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). Safety measures include: neurological deficit, radionecrosis (radiological and clinical), edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula. Efficacy measures include progression-free survival (PFS), overall survival (OS), cognitive function (MoCA Scale), and quality of life (EuroQol scales, EORTC QLQ-HN35, FACT-Br, and TWiST). Methods: Pilot safety and efficacy study in 6 patients compared to 6 controls. 2-year follow-up. A data safety monitoring committee will review the data one month after surgery for each of the first three patients to decide whether to stop or continue the study. Stereotactic biopsy will be performed, and if GBM is diagnosed, patients will undergo conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy and concurrent temozolomide (TMZ). 5 weeks later, patients will undergo supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. 7 days after surgery, maintenance TMZ will be administered for 6 months. The control group will follow standard treatment (Stupp protocol). Data analysis will be performed using non-parametric tests. Samples from successive surgeries will be studied with histology, molecular biology, and cell cultures.

Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

Information on adverse events will be reviewed through direct questioning of the patient.

Information on adverse events will be reviewed through the results of examinations, complementary tests and analytical parameters.

brain RM image, for neuroradiological follow-up

AC_PET image, for neuroradiological follow-up

Progression-free survival (PFS), a measure of how long a patient receives treatment before the cancer begins to grow.

Overall survival (OS), how long patients live after starting treatment.

A commonly used instrument measuring general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL

It has been shown to be useful at detecting cognitive dysfunction in brain metastases.

The test is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory recall (5 points), visuospatial abilities through clock-drawing (3 points) and cube copy (1 point), and orientation (6 points). Executive function is assessed through modified Trail Making Part B (1 point), phonemic fluency (1 point), and verbal abstraction (2 points). A sustained-attention task (1 point), digit span (2 points), and serial calculation (3 points) test attention, concentration, and working memory. And lastly, language is assessed through naming low-familiarity animals (3 points), sentence repetition (2 points), and the fluency task

Asociación de Afectados Por Tumores Cerebrales en España (ASATE)

Hospital San Carlos, Madrid

Professor

Symptoms and General Pathology

Recurrence

Central Nervous System Depressants

Anesthetics

Photosensitizing Agents

Stereotactic biopsy followed by stereotactical photodynamic therapy

5-ALA HCl orally (20 mg/kg bw) 3,5-4,5 hours prior to induction of anaesthesia for stereotactic biopsy followed by stereotactical photodynamic therapy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).

Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid

Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).

Juliane Schroeteler, Dr. med.

Walter Stummer, Univ.-Prof. Dr. med.

In this multicenter, randomized, non-blinded trial the efficacy and safety of stereotactical photodynamic therapy with 5-aminolevulinic acid will be investigated in 106 patients with recurrent glioblastoma.

Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma

Controlled Clinical Trial to Evaluate the Safety and Efficacy of Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma

Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria (Response Assessment in Neuro-Oncology Criteria) or death from any cause

Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria or death from any cause

Overall survival (OS) measured as time from the day of randomization until death

Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)

Response is assessed according to the RANO criteria

Minimum value: 0, maximum value: 100. A higher value means a better outcome.

Minimum value: 0, maximum value: 42. A higher value means a worse outcome.

Minimum value: 0, maximum value: 30. A higher value means a better outcome.

photonamic GmbH & Co. KG

medac GmbH

LifePhotonic GmbH

University Hospital Muenster

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo MRI-guided stereotactic biopsy. Patients then undergo radiosurgery over 1 fraction. Within 14 days, patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.

Patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.

Radiation Therapy

Radiosurgery

Stereotactic Biopsy

Therapeutic Conventional Surgery

Tumor Treating Fields Therapy

Magnetic Resonance Imaging

Biospecimen Collection

Biopsy

Clinical Trial Referral Office

Daniel M. Trifiletti, M.D.

This phase I/IIA trial finds out the possible benefits and/or side effects of radiosurgery before surgery (preoperative) in treating patients with high grade glioma. Radiosurgery uses special equipment to position the patient and precisely give a single large dose of radiation to the tumor. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pre-operative radiosurgery may improve the odds of brain tumor control and reduce treatment-related side effects.

PRIMARY OBJECTIVE:

I. To evaluate the safety of preoperative radiosurgery in the treatment of patients with biopsy-proven high grade glioma prior to conventional therapy.

SECONDARY OBJECTIVES:

I. Acute clinical toxicity profile using Common Terminology Criteria for Adverse Events (CTCAE) version 5 (defined as within 4 weeks of completion of postoperative radiotherapy.

II. Radiographic tumor control at 12 months following surgery (per Response Assessment in Neuro-Oncology \[RANO\] criteria).

III. Rate of pseudoprogression at first post radiation scan (RANO criteria). IV. Overall survival at 12 months following surgery.

CORRELATIVE RESEARCH OBJECTIVE:

I. Evaluation of the tumor repair pathways triggered by radiation, tumor vascular changes, tumor microenvironment immune profiling, cell cultures, and the creation of orthotopic xenograft models for future study.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients undergo magnetic resonance imaging (MRI)-guided stereotactic biopsy. Patients then undergo radiosurgery over 1 fraction. Within 14 days, patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without tumor treating fields (TTF) at the discretion of the treating neuro-oncologist.

COHORT B: Patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist.

Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.

After completion of study treatment, patients are followed up every 2-3 months for up to 5 years.

Preoperative Radiosurgery for the Treatment of High Grade Glioma, The NeoGlioma Study

Preoperative Radiosurgery in High Grade Glioma: A Phase I/IIA Clinical Trial: The NeoGlioma Study

Any excess tissue recovered from the surgical specimen (after standard of care pathologic evaluation) will undergo a series of advanced testing, potentially including but not limited to evaluation of the tumor repair pathways triggered by radiation, tumor vascular changes, tumor microenvironment immune profiling, cell cultures, and the creation of orthotopic xenograft models for future study. Analysis will be completed outside the scope of this protocol.

Assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. The toxicity rate will be estimated using a binomial estimator and a one-sided 95% confidence interval (CI) of the rate will be computed with normal approximation.

Assessed per CTCAE v5.0. The maximum grade for each type of acute adverse events will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.

Assessed per Response Assessment in Neuro-Oncology (RANO) criteria. The cumulative incidence of radiographic tumor recurrence will be estimated using a competing risks method (Gooley et al.) by treatment arm. The competing risks will be death. Comparison between arms will employ Fine-Gray regression.

Assessed per RANO criteria. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the pseudoprogression(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.

Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% CIs. Comparison between arms will employ a log-rank test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Usefulness of Therapy Monitoring by Means of [(18)F]Fluoroethyltyrosine-Positron Emission Tomography (FET-PET) in Glioblastoma Multiforme Patients	NCT01089868	Glioblastoma Mu...		18 Years -	Ludwig-Maximilians - University of Munich
Intraoperative MRI-guidance in Frameless Stereotactic Biopsies	NCT01779219	Primary Brain T...	iMRI-guided bra... Stereotactic fr...	18 Years -	Wroclaw Medical University
A Post-Market Clinical Trial to Evaluate the Performance and Operation of the Brevera Breast Biopsy System	NCT03300206	Breast Cancer F...	Breast Biopsy	18 Years -	Hologic, Inc.
Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma	NCT06418113	Glioblastoma Glioblastoma Mu... Glioblastoma, I... Radiotherapy; C... Cancer Brain	hypofractionate... Stereotactic bi... resection Chemotherapy radiotherapy St... Chemotherapy St...	18 Years - 75 Years	Hospital San Carlos, Madrid
Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma	NCT04469699	Glioblastoma Mu...	Stereotactic bi... Stereotactic bi...	18 Years - 75 Years	University Hospital Muenster
A Post-Market Clinical Trial to Evaluate the Performance and Operation of the Brevera Breast Biopsy System	NCT03300206	Breast Cancer F...	Breast Biopsy	18 Years -	Hologic, Inc.
Preoperative Radiosurgery for the Treatment of High Grade Glioma, The NeoGlioma Study	NCT05030298	Malignant Gliom...	Radiation Thera... Radiosurgery Stereotactic Bi... Temozolomide Therapeutic Con... Tumor Treating ... Magnetic Resona... Biospecimen Col... Biopsy	18 Years -	Mayo Clinic
Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma	NCT04469699	Glioblastoma Mu...	Stereotactic bi... Stereotactic bi...	18 Years - 75 Years	University Hospital Muenster

Spots Global Cancer Trial Database for stereotactic biopsy