Multimodal Imaging Analysis During Treatment With Bevacizumab in Patients With Recurrent Glioblastoma

Glioblastoma Clinical Trial

— IMAGLIO  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02841332
• Other study ID #: 12 050 03
• Status: Terminated
• Phase: N/A
• First received: November 3, 2014
• Last updated: December 18, 2016
• Start date: May 2013
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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:
• 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

Drug:
• Bevacizumab
Administration of bevacizumab during 7 cycles of treatment (J1, J15, J30, J45, J60, J120 and J180)

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

Locations

Country	Name	City	State
France	UHToulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No