Multimodal Imaging Analysis During Treatment With Bevacizumab in Patients With Recurrent Glioblastoma (IMAGLIO)

Multimodal Imaging Analysis of Tissue Changes Occurring During Treatment With Antiangiogenic (Bevacizumab) in Patients With Recurrent Glioblastoma

The purpose of this study is to estimate the capacity of the multimodal imaging parameters measured at 15 days and 2 months of initiation of treatment with bevacizumab, to measure changes in clinical status (sensitivity to measure changes) in patients treated for recurrent glioblastoma.

Study Overview

• Status: Terminated
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: F-MISO; Other: Cerebral magnetic resonance imagery; Drug: Bevacizumab; Other: Clinical examination

Detailed Description

Glioblastomas are tumors with poor prognosis. The treatment of recurrent glioblastoma after a standard first-line treatment is not clearly codified, however, many results in the literature show the benefit of bevacizumab (anti- angiogenic therapy) and it is often proposed in this indication . Tissue action, response mechanisms and therapeutic escape remain is poorly understood.

The investigators hypothesize that these response mechanisms are controlled by changes in some parameters in the tumor tissue, such as hypoxia, neoangiogenesis, cell density and that multimodal imaging can help us to better understand these mechanisms.

To identify which parameters of imaging would best measure response mechanisms, the investigators want to evaluate in the first study and for this particular indication , a property of the measure called by the Anglo -Saxon ' sensitivity to change " that is to say, its sensitivity or ability to measure changes. This is an additional property to the reproducibility of the measurement.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31000
    • UHToulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• World Health Organization performance index lower or equal to 3
• Estimated life expectancy greater than 3 months
• patient in whom the diagnosis of glioblastoma was histologically proven
• Patient with tumor progression of morphological magnetic resonance imagery evidenced by Pluri Disciplinary Meeting. This increase must meet the detailed criteria Response Assessment Neuro Oncology Working group : except in the case of a new lesion appearing outside of the field of radiotherapy, tumor progression can not therefore be defined on an magnetic resonance imagery performed in a period shorter than 12 weeks after the last day of radiotherapy (see criteria Response Assessment Neuro Oncology Working Group detailed chapter 2-1 B)
• Patient with unilateral tensor above injury at baseline (in order to have in each case a tumor region of interest area and an area equivalent region of interest contralateral healthy tissue) .
• Patient with measurable lesion at baseline, according to the criteria defined by the working group Respons Assessment Neuro Oncology. The lesion with contrast is measured two-dimensionally on T1 gadolinium in axial section. The two perpendicular diameters of red lead should be 10 mm and that at least two axial sections.
• Patient with progression after radiotherapy and have received at least one chemotherapy regimen (temodal)
• A patient in whom treatment with bevacizumab monotherapy

Exclusion Criteria:

• Pregnancy
• Exclusion criteria related to cons to the realization of positron emission tomography or magnetic resonance imagery : Weight greater than 120 kg, Foreign body incompatible with magnetic resonance imagery (eg metallic intraocular foreign body), Medical equipment installed incompatible with magnetic resonance imagery (eg pacemaker)
• Pregnant or lactating woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with glioblastoma; Patient with histologically proved glioblastoma diagnostic will receive the following interventions : Cerebral magnetic resonance imagery; Tomography emission positron with F-MISO; Bevacizumab administration; Clinical examination

Drug: F-MISO; The fluoro-misonidazole is a positron emission tomography tracer (labeled with Fluorine-18)-specific hypoxia. This compound penetrates into cells where it is reduced by a nitroreductase enzyme. It is rapidly regenerated by reoxidation when the cell is properly oxygenated. This metabolite can accumulate in viable hypoxic cells (necrotic cells that can provide initial reduction reaction of F-MISO). Moreover, the fixing of this tracer appears to be independent of blood flow. The advantage of this technique is to provide a direct image of hypoxic cells by directly targeting under stress hypoxic.; Other Names: fluoro-misonidazole; Other: Cerebral magnetic resonance imagery; During the pre-therapeutic imagery session : Morphological magnetic resonance imagery ( axial T1 sequence axial T1 post contrast , Flair Axial ); magnetic resonance imagery spectroscopy sequence; Perfusion magnetic resonance imagery sequence; Diffusion magnetic resonance imagery sequence; Other Names: Cerebral MRI; Drug: Bevacizumab; Administration of bevacizumab during 7 cycles of treatment (J1, J15, J30, J45, J60, J120 and J180); Other Names: Avastin; Other: Clinical examination; During the examination, the following parameters will be checked : Neurological examination; Corticotherapy prescribed; General status of patient (world health organization score); Weight and height; Control of arterial pressure; Chirurgical and medical history; Concomitant treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection capacity of patient clinical status in imagery with F-MISO as assessed by tomography with emission of positron	Specific imagery parameters used are : Standard Uptake Value max, mean Standard Uptake Value, global or tumoral volume reported	At day 15 after the 1st perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Perfusion magnetic resonance imagery	Specific imagery parameters used are : Cerebral blood volume and relative cerebral blood volume, absolute neo angiogenesis and reported to tumoral volume	At day 15 after the 1st perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Diffusion magnetic resonance imagery	Specific imagery parameters used are : Apparent diffusion Coefficient and Apparent diffusion relative Coefficient , absolute elevated cellular density volume and reported to tumoral volume	At day 15 after the 1st perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Spectroscopy magnetic resonance imagery	Specific imagery parameters used are : choline pike, NAA pike, mean and maximal creatinine pike, mean and maximal ratio choline/NAA, mean and maximal ratio choline/creatinine	At day 15 after the 1st perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by tomography with emission of positron	Specific imagery parameters used are : Standard Uptake Value max, mean Standard Uptake Value, global or tumoral volume reported	At day 60 after the 4th perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Perfusion magnetic resonance imagery	Specific imagery parameters used are : Cerebral blood volume and crelative cerebral blood volume, absolute neo angiogenesis and reported to tumoral volume	At day 60 after the 4th perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Diffusion magnetic resonance imagery	Specific imagery parameters used are : Apparent diffusion Coefficient and Apparent diffusion relative Coefficient , absolute elevated cellular density volume and reported to tumoral volume	At day 60 after the 4th perfusion of bevacizumab
Detection capacity of patient clinical status in imagery with F-MISO as assessed by Spectroscopy magnetic resonance imagery	Specific imagery parameters used are : choline pike, NAA pike, mean and maximal creatinine pike, mean and maximal ratio choline/NAA, mean and maximal ratio choline/creatinine	At day 60 after the 4th perfusion of bevacizumab

Secondary Outcome Measures

Outcome Measure	Time Frame
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with relative cerebral blood volume in Perfusion magnetic resonance imagery	at day 15 after the 1st perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with relative cerebral blood volume in Perfusion magnetic resonance imagery	at day 60 after the 4th perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with apparent diffusion coefficient on diffusion magnetic resonance imagery	at day 15 after the 1st perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with apparent diffusion coefficient on diffusion magnetic resonance imagery	at day 60 after the 4th perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of choline on spectroscopy magnetic resonance imagery	at day 15 after the 1st perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of choline on spectroscopy magnetic resonance imagery	at day 60 after the 4th perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of N-acetyl aspartate on spectroscopy magnetic resonance imagery	at day 15 after the 1st perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of N-acetyl aspartate on spectroscopy magnetic resonance imagery	at day 60 after the 4th perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of rate of creatinine on spectroscopy magnetic resonance imagery	at day 15 after the 1st perfusion of bevacizumab
Estimation of predictive parameters of progression free survival with a sensibility of change of at least 75% as assessed with rate of rate of creatinine on spectroscopy magnetic resonance imagery	at day 60 after the 4th perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by relative cerebral blood volume in Perfusion magnetic resonance imagery	At day 15 after the first perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by relative cerebral blood volume in Perfusion magnetic resonance imagery	At day 60 after the 4th perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by apparent diffusion coefficient on diffusion magnetic resonance imagery,	At day 15 after the 1st perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by apparent diffusion coefficient on diffusion magnetic resonance imagery,	At day 60 after the 4th perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by rate of choline on spectroscopy magnetic resonance imagery	At day 15 after the 1st perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by rate of choline on spectroscopy magnetic resonance imagery	At day 60 after the 4th perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by N-acetyl aspartate on spectroscopy magnetic resonance imagery	At day 15 after the 1st perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by N-acetyl aspartate on spectroscopy magnetic resonance imagery	At day 60 after the 4th perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed byrate of creatinine on spectroscopy magnetic resonance imagery	At day 15 after the 1st perfusion of bevacizumab
Estimation of imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% as assessed by rate of creatinine on spectroscopy magnetic resonance imagery	At day 60 after the 4th perfusion of bevacizumab
Variation in imagery predictive parameters for progression free survival with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by relative cerebral blood volume in Perfusion magnetic resonance imagery	At day 15 and day 60
Variation in imagery predictive parameters for progression free survival with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by apparent diffusion coefficient on diffusion magnetic resonance imagery	At day 15 and day 60
Variation in imagery predictive parameters for progression free survival with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by rate of choline on spectroscopy magnetic resonance imagery	At day 15 and day 60
Variation in imagery predictive parameters for progression free survival with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by N-acetyl aspartate on spectroscopy magnetic resonance imagery	At day 15 and day 60
Variation in imagery predictive parameters for progression free survival with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by rate of creatinine on spectroscopy magnetic resonance imagery	At day 15 and day 60
Variation in imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by relative cerebral blood volume in Perfusion magnetic resonance imagery	At day 15 and day 60
Variation in imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by apparent diffusion coefficient on diffusion magnetic resonance imagery	At day 15 and day 60
Variation in imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by rate of choline on spectroscopy magnetic resonance imagery	At day 15 and day 60
Variation in imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by rate of N-acetyl aspartate on spectroscopy magnetic resonance imagery	At day 15 and day 60
Variation in imagery prognostic parameters for global survival at 6 months with a sensibility of change of at least 75% between cycle 1 and cycle 4 of treatment as assessed by rate of creatinine on spectroscopy magnetic resonance imagery	At day 15 and day 60

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Alexandra Benouaich-Amiel, MD, U H Toulouse

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: November 3, 2014
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimate): July 22, 2016

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: December 18, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Recurrent Glioblastoma; Positron emission tomography; Fluoro misonidazole; MRI multimodal
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Bevacizumab; Misonidazole
• Other Study ID Numbers: 12 050 03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No