Early Diagnosis of Pseudoprogression Using 11C-Methionine PET-MRI After Concomitant Radiochemotherapy Treatment for Glioblastoma. (TIGRE)

Pseudoprogression is a phenomenon related to post-treatment rearrangements (including radiation necrosis). It appears early in the first year after treatment and accounts for 30 to 50% of patients followed with glioblastoma. On MRI (current gold standard with international therapeutic response evaluation criteria RANO 2010), pseudoprogression is manifested by a progression of morphological abnormalities (contrast enhancement, FLAIR hypersignal) and can simulate tumor recurrence, even though the corticosteroid improved or kept clinical symptoms stabilized. In view of prognosis, the current diagnostic tools have not enough diagnosis accuracy for differentiation between pseudo-progression and early tumor recurrence, and are based on MRI retrospective analysis (2-3 months after). Recurrence of glioblastoma, is characterized by a higher amino acid metabolism than pseudoprogression, also 11C-Methionine (11C-MET), positron emitting radiotracer, showed promising results to differentiate these two entities. To date, hybrid 11C-MET PET-MRI studies remains limited to small sample size (a few dozen patients), and none focuses exclusively on glioblastoma.

Hypothesis of our study is that 11C-MET PET-MRI may be performed as a first-line MRI for suspected pseudoprogression and may changes therapeutic decision making and also patient prognosis.

The main objective is to evaluate the performance of hybrid PET-MRI imaging with 11C-MET to differentiate pseudoprogression from glioblastoma recurrence in patients treated with surgery and radiochemotherapy, compared to multimodality MRI).

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Other: 11C-Methionine PET-MRI

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: DUCRAY François, MD; Phone Number: 00 (33) 4 72 68 13 21; Email: francois.ducray@chu-lyon.fr
• Study Contact Backup: Name: ISAL Sibel, MD; Phone Number: 00 (33) 4 72 35 76 29; Email: sibel.isal@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69 677
    • Recruiting
    • Hopices Civils de Lyon
    • Contact: DUCRAY François, MD; Phone Number: 00 (33) 4 72 68 13 21; Email: francois.ducray@chu-lyon.fr
    • Contact: ISAL Sibel, MD; Phone Number: 00 (33) 4 72 35 76 29; Email: sibel.isal@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 or over,
• Patient with glioblastoma treated by radiochemotherapy with temozolomide,
• Patient with suspicion of pseudoprogression between the 1st and 12th month after the end of concomitant chemoradiotherapy,
• Patient receiving a social security scheme,
• Patient for whom informed and written consent to participate has been obtained,

Exclusion Criteria:

• Subject under safeguard of justice (tutelage, curatorship),
• Minor patient,
• Patient without signs of progression MRI (stable disease or good response to treatment according to the RANO 2010 criteria),
• Clinical or radiological progression justifying a change of treatment,
• Patient not able to decide and with refusal of the family entitled to continue research.
• Pregnant woman, breastfeeding or old enough to have children but without effective contraception,
• Contraindication to performing an MRI: permanently fixed metal parts (pacemaker, cerebral clip, cochlear implant, pin or screw for recent bone fracture, dental equipment, metal splinters), claustrophobia,
• Contraindication to gadolinium according to ANSM 2017 recommendations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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; implementation of 11C-Methionine PET-MRI	Other: 11C-Methionine PET-MRI; Implementation 11C-Methionine PET-MRI performed for each patient in one place (department of nuclear medicine of Hospices Civils de Lyon). The 11C-Methionine PET-MRI will be performed after radiochemotherapy in patients with MRI suspicious of pseudoprogression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
false negatives and false positives description (diagnosis accuracy) of 11C-Methionine PET-MRI	diagnosis accuracy of 11C-MET PET-MRI to differentiated pseudoprogression from tumor recurrence, compared to MRI. The gold-standard being retrospective MRI analysis.	within 1 months and 12 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ROC curves for comparison of two diagnostic tests: MRI and PET-MRI	use of area under the curve for each tests to identify the best	within 1 months and 24 months after inclusion
The proportion of pseudoprogression identified by PET-MRI to 11C-MET according to the genetic data	The proportion of pseudoprogression identified by PET-MRI to 11C-MET according to the methylation status of the O6-methylguanine-DNA- methyltransferase (MGMT) promoter, the level of expression of isocitrate dehydrogenase (IDH) mutation, ki67 and 1p19q mutation.	during 24 months after inclusion
Overall survival analysis	Patients will be followed regularly for 2 years to assess overall survival at 12 months and at 24 months.	during 24 months after inclusion

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: DUCRAY François, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2019
• Primary Completion (Anticipated): February 26, 2020
• Study Completion (Anticipated): January 26, 2025

Study Registration Dates

• First Submitted: November 6, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: radiotherapy; glioblastoma; sensitivity; temozolomide; 11C-Methionine PET-MRI
• 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; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Carbon-11 methionine
• Other Study ID Numbers: 69HCL18_0265; 2018-002016-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No