Impact of [11C]-Methionine PET/MRI for Individual Tailoring Postoperative Radiochemotherapy for Glioblastoma Multiforme

• ClinicalTrials.gov Identifier: NCT01873469
• Recruitment Status: Completed
• First Posted: June 10, 2013
• Last Update Posted: February 18, 2019
• Sponsor: Technische Universität Dresden
• Information provided by (Responsible Party): Mechthild Krause, Technische Universität Dresden

Study Description

Brief Summary:

Local recurrence is a major problem of clinical treatment of glioblastoma multiforme (GBM). Today a very sensitive imaging method to detect glioblastoma is [11C]MET Positron emission tomography (PET), where in some patients also tumour manifestations can be detected that are not visible in MRI investigations.

The aim of the study is to investigate the association of high [11C]MET tracer uptake before postoperative radiochemotherapy and concurrent temozolomide (TMZ) with time to recurrence in patients with glioblastoma multiforme. Also site of recurrence will be correlated with the [11C]MET imaging before and early during radiochemotherapy. All imaging information will be included in treatment planning or treatment decisions.

The study provides a basis for later radiation dose escalation trials on the base of [11C]MET imaging.

Condition or disease	Intervention/treatment
Glioblastoma Multiforme	Radiation: Radiochemotherapy

Detailed Description:

The current study aims to investigate the association of high [11C]MET tracer uptake before postoperative radiochemotherapy and concurrent temozolomide (TMZ) with time to recurrence in patients with glioblastoma multiforme (GBM).

[11C]MET-PET is expected to provide diagnostic (quantitative and spatial information) as well as prognostic information, to monitor treatment, to help stratification of patients for radiotherapeutic interventions such as dose-painting in order to optimize clinical applications and potentially improve the treatment outcome.

This study aims to provide the basis (e.g. optimal threshold value, sensitivity, specificity of MET uptake) for later intervention trials for treatment intensification, e.g. proton boost irradiation based on specific biomarkers.

The trial is a one-arm single-center, non-randomized observational (biomarker) study. After resection or biopsy, patients with newly diagnosed glioblastoma multiforme will receive a [11C]MET-PET/MRI scan before start of concurrent radiochemotherapy (~1-4 weeks after surgery). A fusion with the planning CT for irradiation treatment planning will be performed. Postoperative radiotherapy will be applied in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total dose of 60 Gy (50 Gy and a boost of 10 Gy), with concomitant administration of daily Temozolomide (75 mg/m2 p.o.) from the 1st day to the last day of radiotherapy. Follow up with [11C]MET-PET/MRI will be performed every 3 months until recurrence or until death of the patient.

The uptake of [11C]MET-PET (as standard uptake value - SUV) in tumour and in normal contralateral grey matter before start of concurrent radiochemotherapy will be determined. For each tumour, the ratio between tracer uptake in the tumor and contralateral gray matter will be calculated (lesion-to-gray matter ratio [l/g]).

Primary end point will be time to recurrence (TTR) as function of [11C]MET uptake before chemoradiotherapy. Secondary endpoints will be overall survival; toxicity; C-Index/ROC curve (sensitivity, specificity, optimal threshold for normal/tumour tissue index), necrosis rate; site of recurrence.

The primary analysis will use the Cox proportional hazard model to establish the linear association between [11C]-MET and time-to-recurrence using a one-sided alpha = 0.1.

Parallel translational studies with orthotopic GBM xenografts (generated from the patients material in the trial) in nude mice will be performed in our laboratory to evaluate [11C]MET-PET as a tool for tailoring high precision radiotherapy. Histological, biological and genetic studies are planned to validate the imaging finding and to explore the underlying mechanisms.

Study Design

• Study Type: Observational
• Actual Enrollment: 102 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Observational Study of Impact of [11C]-Methionine PET/MRI as a Tool for Individual Tailoring Postoperative Radiochemotherapy for Patients With Glioblastoma Multiforme
• Study Start Date: July 2013
• Actual Primary Completion Date: October 2017
• Actual Study Completion Date: October 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
Radiochemotherapy; glioblastoma patients with indication to radiochemotherapy	Radiation: Radiochemotherapy; postoperative radiochemotherapy 60 Gy/ Temozolomide

Outcome Measures

Primary Outcome Measures :

1. Time to recurrence as function of [11C]MET uptake before postoperative radiochemotherapy [ Time Frame: participants will be followed until tumour recurrence, an expected average of 7 months ]

Secondary Outcome Measures :

1. overall survival [ Time Frame: expected average 15 months ]

Biospecimen Retention:   Samples With DNA

fresh tumour pieces, blood samples

Eligibility Criteria

• 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

Patients with the diagnosis of glioblastoma multiforme

Criteria

Inclusion Criteria:

• histologically confirmed newly diagnosed glioblastoma multiforme
• macroscopic total tumour resection or biopsy
• indication for combined radiochemotherapy with temozolomide
• patients are allowed to take part in other clinical trials at the same time
• beginning of radiochemotherapy no later than 7 weeks after surgery
• Karnofsky Performance Score ≥ 60, ECOG ≤2
• women with childbearing potential, (and men) adequate contraception
• ability of subject to understand character and individual consequences of the clinical trial
• written informed consent

Exclusion Criteria:

• previous radiotherapy of the brain or chemotherapy with TMZ other than during the radiochemotherapy
• time interval of > 7 weeks after surgery and beginning of radiochemotherapy
• patients who are not suitable for radiochemotherapy
• known other malignant disease that impacts prognosis of the patient and/or is likely to require treatment interfering with study therapy
• pregnant or lactating women
• patients with non-MRI compatible metal implants, pacemaker or non-MRI compatible external automatic defibrillators, insulin pumps, neurostimulators, cochlear implants
• Claustrophobic patients
• refusal of the patients to take part in the study

Contacts and Locations

Locations

Germany

Dresden University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Oncology; and DKTK partner site Dresden

Dresden, Saxony, Germany, 01307

Sponsors and Collaborators

Technische Universität Dresden

Investigators

• Study Chair: Mechthild Krause, MD; Dresden University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology; and DKTK partner site Dresden

More Information

• Responsible Party: Mechthild Krause, PD Dr. med., Technische Universität Dresden
• ClinicalTrials.gov Identifier: NCT01873469
• Other Study ID Numbers: STR-PETra-2013
• First Posted: June 10, 2013
• Last Update Posted: February 18, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Mechthild Krause, Technische Universität Dresden:

glioblastoma multiforme; radiotherapy

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