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

May 21, 2019 updated by: Juan M Garcia-Gomez

Multicentre Validation of Hemodynamic Multiparametric Tissue Signature (MTS) Biomarkers From Preoperative and Postradiotherapy MRI in Patients With Glioblastoma: Predictors of Overall Survival

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.

Study Overview

Status

Completed

Conditions

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

Enrollment (Actual)

305

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valencia, Spain, 46022
        • Universitat Politècnica de València

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From the date of the first MRI acquisition until the date of death from any cause, assessed up to 80 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From the date of the first MRI acquisition until the date of first documented progression, assessed up to 80 months
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.
From the date of the first MRI acquisition until the date of death from any cause, assessed up to 80 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Juan M Garcia-Gomez

Collaborators

Oslo University Hospital
Hospital Clinic of Barcelona
University of Liege
Hospital de Manises
Azienda Ospedaliero-Universitaria di Parma
Hospital Vall d'Hebron
Hospital de la Ribera

Investigators

  • Principal Investigator: Juan M Garcia Gomez, PhD, Universitat Politècnica de València

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2018

Primary Completion (Actual)

July 1, 2018

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

February 7, 2018

First Submitted That Met QC Criteria

February 19, 2018

First Posted (Actual)

February 20, 2018

Study Record Updates

Last Update Posted (Actual)

May 22, 2019

Last Update Submitted That Met QC Criteria

May 21, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPV-2018-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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