Image Guided Reirradiation of High-grade Glioma

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the short- and long term toxicity of radiotherapy to patients with recurrent high-grade glioma who have previously received radiotherapy and to determine the best dose and treatment regimen. Positron emission tomography (PET) using an amino acid tracer, 18-fluoro-ethyltyrosine (18F-FET), is used for target delineation.The study examines, in four sequential treatment groups, the effect of dose, hypofractionation and treatment volume on toxicity. Upon completion of the phase I part, the study progresses to phase II where the best dose- and treatment regimen will be chosen for treatment.

Official Title
-----------------
Image Guided Reirradiation of High-grade Glioma - a Phase I/II Dose Escalation Study

Conditions
-----------------
Malignant Glioma, Glioblastoma

Intervention / Treatment
-----------------
* Radiation: External beam radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: recurrent high-grade glioma previous focal radiotherapy for high-grade glioma no standard treatment options available/indicated ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1 or 2 life expectancy > 3 months hemoglobin value > 6 mmol/l (transfusion permitted) able to understand oral and written Danish Exclusion Criteria: disseminated recurrent disease infection or wound dehiscence or other pathological condition in meninges/skull/scalp symptoms of elevated intracranial pressure very early recurrence following primary radiotherapy (< or equal to 3 months) contraindications to magnetic resonance imaging (MRI) or positron emission tomography (PET) other previous radiotherapy to the brain than primary course of irradiation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: External beam radiotherapy<br>Hypofractionated external beam radiation delivered in 4 different sequential dose/fractionation groups. | Radiation: External beam radiotherapy<br>* Study group 1: 3.5 Gray x 10, 5 fractions per week. Study group 2: 3.5 Gray x 10 + 7 Gray boost to biological target volume, 5 fractions per week. Study group 3: 5.9 Gray x 10, 5 fractions per week. Study group 4 (planning target volumes: 100 millilitres - 300 millilitres): 3.5 Gray x 10, 5 fractions per week. Phase II dosis: to be chosen based on results of phase I study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Early (<4 weeks) and late (> 4 weeks) toxicity evaluated by Common Toxicity Criteria ver. 3.0 at multiple time points up to one year after treatment. (for phase I part of the study) | One year | 
| Diagnostic precision of 18F-FET-PET imaging in recurrent high-grade glioma | Diagnostic accuracy (positive- and negative predictive value) of 18F-FET-PET guided biopsies (optional procedure) in patients who will receive reirradiation for recurrent high-grade glioma in the study. (for phase I part of the study). | Approximately one to two weeks prior to radiotherapy | 
| Time to neurocognitive decline | Time to neurocognitive decline assessed using a test battery comprised of validated tests at multiple time points. (for phase II part of the study) | Up to one year | 
| Time to progression | Time to disease progression evaluated by RANO (Response Assessment in Neuro-Oncology) criteria (for phase II part of the study). | Up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of 18F-FET-PET in reirradiation of high-grade glioma | Prognostic value of 18F-FET-PET scan at baseline, value of 18F-FET-PET as an early response marker and correlations between 18F-FET-PET scans and magnetic resonance imaging. | One year | 
| Objective response rate | Rate of objective tumor responses following treatment evaluated by RANO criteria and by 18F-FET-PET. | Up to one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
reirradiation, recurrent glioma, positron emission tomography, amino acid tracer