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Multicentre Validation of How Vascular Biomarkers From Tumor Can Predict the Survival of the Patient With Glioblastoma (ONCOhabitats)

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ClinicalTrials.gov Identifier: NCT03439332
Recruitment Status : Active, not recruiting
First Posted : February 20, 2018
Last Update Posted : October 12, 2018
Sponsor:
Collaborators:
University Hospital of Liege
Hospital de Manises
Hospital de la Ribera
Hospital Vall d'Hebron
Hospital Clinic of Barcelona
Azienda Ospedaliero-Universitaria di Parma
Oslo University Hospital
Information provided by (Responsible Party):
Juan M Garcia-Gomez, Universitat Politècnica de València

Brief Summary:

Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The relationship between non-invasive Magnetic Resonance Imaging (MRI) biomarkers at preoperative, postradiotherapy and follow-up stages, and the survival time in GBM patients will be useful to plan an optimal strategy for the management of the disease.

The Hemodynamic Multiparametric Tissue Signature (HTS) biomarker provides an automated unsupervised method to describe the heterogeneity of the enhancing tumor and edema areas in terms of the angiogenic process located at these regions. This allows to automatically draw 4 reproducible habitats that describe the tumor vascular heterogeneity:

  • The High Angiogenic enhancing Tumor (HAT)
  • The Less Angiogenic enhancing Tumor (LAT)
  • The potentially tumor Infiltrated Peripheral Edema (IPE)
  • The Vasogenic Peripheral Edema (VPE)

The conceptual hypothesis is that there is a significant correlation between the perfusion biomarkers located at several HTS habitats and the patient's overall survival.

The primary purpose of this clinical study is to determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using the HTS biomarker.


Condition or disease
Glioblastoma

Detailed Description:

This is a multicenter observational retrospective study with data collected from Hospital Information System (HIS) and Picture Archiving and Communication System (PACS) of each center involved in the study. The cohort is built with patients diagnosed with glioblastoma (GBM) with a Magnetic Resonance Imaging (MRI) pre-treatment since 1st of January of 2012 until the Study Start Date.

The main objective of the study is to determine if the habitats obtained by the Hemodynamic Multiparametric Tissue Signature (HTS) biomarker, which describe the tumor vascular heterogeneity of the enhancing tumor and edema areas, are predictive of the overall survival of patients undergoing standard-of-care treatment.

The specific objectives of the study are:

  • To identify four habitats within the GBM using MRI and HTS
  • To analyse the relation between the HTS habitats obtained from the first preoperative MRI and the overall survival of the patient
  • To analyse the relation between HTS habitats obtained from the first preoperative MRI and the progression-free survival of the patient
  • To analyse the relation between the HTS habitats obtained from the postradiotherapy MRI and the overall survival of the patient
  • To analyse the relation between HTS habitats obtained from the postradiotherapy MRI and the progression-free survival of the patient
  • To discover other interesting relations between the HTS habitats obtained from preoperative, postradiotherapy and follow-up images and the clinical conditions of the patients

Cox regression, Kaplan-Meier estimator and multiple linear regression analysis will be used to assess survival significance of each biomarker at each HTS habitat. The predictive value will be compared with models based on clinical and volumetric image variables: Age, Karnofsky Performance Status (KPS) Scale and Visually AcceSAble Rembrandt Images (VASARI) features. Moreover, the HTS-based models will be compared to models based on hemodynamic biomarkers, such as Cerebral Blood Flow (CBF), Cerebral Blood Volume (CBV), capillary permeability (Ktrans) and fractional Volume of Extravascular-Extracellular space (Ve), and diffusion biomarkers, such as Apparent Diffusion Coefficient (ADC), extracted from automatic segmentations of the edema and the enhancing tumor. Finally, Sørensen-Dice coefficient will be used to measure the correlation between MTS habitats in longitudinal studies.


Study Type : Observational
Actual Enrollment : 305 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Multicentre Validation of Hemodynamic Multiparametric Tissue Signature (MTS) Biomarkers From Preoperative and Postradiotherapy MRI in Patients With Glioblastoma: Predictors of Overall Survival
Actual Study Start Date : February 7, 2018
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Correlation between overall survival (in days) of patients undergoing standard-of-care treatment and the tumor vascular heterogeneity described by the four habitats obtained by the Hemodynamic Multiparametric Tissue Signature (HTS) biomarker [ Time Frame: From the date of the first MRI acquisition until the date of death from any cause, assessed up to 80 months ]
    The overall survival for each patient is estimated since the date of the preoperative Magnetic Resonance Imaging (MRI) to the exitus date. Exitus date will be collected from clinical records and should be confirmed by the main investigator from each center.


Secondary Outcome Measures :
  1. Correlation between progression-free survival (in days) of patients undergoing standard-of-care treatment and the tumor vascular heterogeneity described by the four habitats obtained by the HTS biomarker [ Time Frame: From the date of the first MRI acquisition until the date of first documented progression, assessed up to 80 months ]
    The progression-free survival for each patient is estimated since the date of the preoperative MRI to the date of recurrence.

  2. Correlation between MTS habitats in longitudinal studies [ Time Frame: From the date of the first MRI acquisition until the date of death from any cause, assessed up to 80 months ]
    In order to study this outcome, the postradiotherapy and the follow-up images in combination with the preoperative ones, will be used.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The population of the target group is formed by patients diagnosed with Glioblastoma grade IV World Health Organization (WHO) with histopathological confirmation
Criteria

Inclusion Criteria:

  • Patients diagnosed with Glioblastoma grade IV WHO with histopathological confirmation
  • Age >18 years at diagnosis
  • Patients with access to the preoperative and postradiotherapy MRI studies using 1.5 Tesla (T) or 3T scanners, including: pre and post gadolinium T1-weighted MRI, T2-weighted MRI, FLAIR MRI, Dynamic Susceptibility Contrast (DSC) T2*-weighted perfusion, Dynamic Contrast Enhancement (DCE) T1-weighted perfusion (optional) and Diffusion Weighted Imaging (DWI) (optional)
  • WHO performance score between 0 and 2
  • Patients with Karnofsky Performance Score (KPS) of ≥ 70%

Exclusion Criteria:

  • Patients with congestive heart failure within 6 months prior to study entry (New York Heart Association ≥ Grade 3)
  • Uncontrolled or significant cardiovascular disease, including: myocardial infarction and transient ischemic attack or stroke within 6 months prior to enrollment, uncontrolled angina within 6 months, diagnosed or suspected congenital long QT syndrome, any history of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes) and clinically significant abnormality on electrocardiogram (ECG)
  • Pulmonary disease including or greater than grade 2 dyspnea or laryngeal edema, grade 3 pulmonary edema or pulmonary hypertension according to CTCAE 4.03

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439332


Locations
Spain
Universitat Politècnica de València
Valencia, Spain, 46022
Sponsors and Collaborators
Juan M Garcia-Gomez
University Hospital of Liege
Hospital de Manises
Hospital de la Ribera
Hospital Vall d'Hebron
Hospital Clinic of Barcelona
Azienda Ospedaliero-Universitaria di Parma
Oslo University Hospital
Investigators
Principal Investigator: Juan M Garcia Gomez, PhD Universitat Politècnica de València
  Study Documents (Full-Text)

Documents provided by Juan M Garcia-Gomez, Universitat Politècnica de València:

Additional Information:
Publications:
Responsible Party: Juan M Garcia-Gomez, Associate Professor, PhD, Universitat Politècnica de València
ClinicalTrials.gov Identifier: NCT03439332     History of Changes
Other Study ID Numbers: UPV-2018-001
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juan M Garcia-Gomez, Universitat Politècnica de València:
Highly infiltrative
Deeply invasive
Strong vascular proliferation
Robust angiogenesis
Vascular heterogeneity
Perfusion Biormarker
Non-Invasive Biomarker
Predictor of overall survival
Predictor of progression-free survival

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue