Amino-acid PET Versus MRI Guided Re-irradiation in Patients With Recurrent Glioblastoma Multiforme - Full Text View

Purpose

This study is designed to evaluate the impact of radiotherapy target volume delineation based on AA-PET compared to target volume delineation based on contrast enhanced T1 weighted MRI (T1Gd-MRI) on the clinical outcome of patients with recurrent glioblastoma (GBM) as well as concerning therapeutic safety of the respective strategy.

Condition	Intervention	Phase
Recurrent Glioma (Glioblastoma Multiforme)	Radiation: Radiation Therapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Amino-acid PET Versus MRI Guided Re-irradiation in Patients With Recurrent Glioblastoma Multiforme - a Randomised Phase II Trial

Resource links provided by NLM:

Drug Information available for: Amino acids

U.S. FDA Resources

Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:

Progression Free Survival (PFS) [ Time Frame: 6 months after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 1 year after randomisation ] [ Designated as safety issue: No ]
Kaplan-Meier: Performed on the per protocol population - all patients who are eligible and have started their allocated treatment
Volumetrical assessment of GTV and PTV [ Time Frame: Interim analysis ] [ Designated as safety issue: No ]
Volumetrical assessment of delineated gross tumor volume (GTV) and planning target volume (PTV) based on AA-PET vs. delineated GTV/PTV based on T1-Gd-MRI.
Topography of recurrence [ Time Frame: Follow up (end of radiotherapy, 6 and 12 weeks after radiotherapy, then every 3 months) ] [ Designated as safety issue: No ]
local relationship between recurrence and AA-PEt and MRI-derived TV
Localisation of necrosis after re-irradiation [ Time Frame: Follow up (end of radiotherapy, 6 and 12 weeks after radiotherapy, then every 3 months) ] [ Designated as safety issue: Yes ]
Rate of long-term survivors [ Time Frame: Follow up ] [ Designated as safety issue: No ]
Rate of long-term survivors = Survivors > 1 year after randomisation
Quality of Life (QoL) [ Time Frame: During Radiotherapy and Follow Up ] [ Designated as safety issue: No ]
QoL assessed by the EORTC QlQ-C 15 PAL questionnaire
Rate of side effects [ Time Frame: During Radiotherapy and Follow Up ] [ Designated as safety issue: Yes ]
Assessed according to CTCAE

Estimated Enrollment:	200
Study Start Date:	July 2011
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A: AA-PET based target volume delineation Experimental intervention (Arm A): High-precision re-irradiation. Target volume delineation based on AA-PET.	Radiation: Radiation Therapy Experimental intervention (Arm A): High-precision re-irradiation (stereotactic fractionated radiation therapy (SFRT) and/or image guided radiation therapy, (IGRT), total dose 39 Gy, 3 Gy/d, 5x/ week. Target volume delineation based on AA-PET: GTV = AA uptake on PET, clinical target volume (CTV) = GTV+3mm, PTV = CTV+2mm
Active Comparator: Arm B: T1Gd-MRI based target volume delineation Control intervention (Arm B): High-precision re-irradiation. Target volume delineation based on T1Gd-MRI.	Radiation: Radiation Therapy Control intervention (Arm B): High-precision re-irradiation (SFRT and/or IGRT), total dose 39 Gy, 3 Gy/d, 5x/ week. Target volume delineation based on T1Gd-MRI: GTV = contrast enhancement on T1Gd-MRI, CTV = GTV+3mm, PTV = CTV+2mm

Detailed Description:

The higher sensitivity and specificity of amino-acids (L-[methyl-11C]-methionine, MET and O-(2-(1)-Fluoroethyl)-L-tyrosine, FET) positron emission tomography (AA-PET) in the diagnosis of gliomas in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) was demonstrated in many studies and is the rationale for using them in target volume delineation of these tumors. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI in gross tumor volume (GTV) delineation for treatment planning.

A small prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET or single photon emission tomography (AA-SPECT) were integrated in target volume delineation, in comparison to patients treated using CT/MRI alone (Grosu et al. 2005).

However, there are no randomized studies demonstrating the impact of AA-PET based irradiation treatment on the clinical follow-up in comparison to a traditional MRI/CT based treatment.

The goal of this study is to evaluate the impact of radiotherapy target volume delineation based on AA-PET (new strategy) on the clinical outcome of patients with recurrent glioblastoma (GBM) compared to target volume delineation based on contrast enhanced T1 weighted MRI (T1Gd-MRI) (traditional, established strategy). Concerning therapeutic safety, the topography of recurrence outside the primary target volume as well as the localization of necrosis after the re-irradiation will be determined. All side effects will be assessed by CTCAE version 4.0 and the safety analyses will present the worst grade of acute and late side effect by treatment arm for the whole study period (treatment and follow up). Patients will be asked to complete a quality of life (QoL) questionnaire (as assessed by the E-ORTC QLQ-C15 PAL) in regular time intervals.

This will be the first phase II randomized study evaluating the impact of molecular imaging on outcome after radiotherapy in brain tumor patients.

Another goal of the technical part of this study is the development of a standardized physical-technical methodology for the integration of AA-PET and other imaging biomarkers in tumor volume delineation in radiation therapy.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Local recurrence of GBM (WHO grade IV) and either not eligible for tumor resection or with macroscopic residual tumor after resection of recurrent GBM
Recurrent tumor visible on AA-PET and MRI-T1-Gd with the diameter measuring 1 cm to 6 cm by either technique
Target volume definition possible according to both study arms
Previous radiation therapy of the primary with a maximal total dose 60 Gy
At least 9 months since the end of pre-irradiation and randomisation
At most 2 prior chemotherapy regimes
Start of radiation therapy possible within 2 weeks from AA-PET
Karnofsky Performance Score (KPS) ≥ 70%
Age ≥ 18 years
Written informed consent (IC) obtained

Exclusion Criteria:

- No histological confirmation of Glioma at initial diagnosis)
Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence
No recurrent tumor detectable on last AA-PET or MRI-T1-Gd
Technical impossibility to use existing AA-PET for RT-planning
No prior radiation treatment to the primary tumor
less than 9 months between the end of first radiation treatment and randomisation
more than 2 previous chemotherapy regimes or previous treatment with Avastin or other molecular targeted therapies
less than 2 weeks between application of chemotherapy and randomisation
additional chemotherapy or molecular targeted therapy or further surgery planned before diagnosis of further tumor progression after study intervention
pregnancy, nursing or patient not willing to prevent pregnancy during treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252459

Contacts

Contact: Anca-Ligia Grosu, Prof. Dr. med.	0049-761-270 ext 9520	gliaa@uniklinik-freiburg.de
Contact: Ursula Nestle, PD Dr. med.	0049-761-270 ext 9520	gliaa@uniklinik-freiburg.de

Locations

Germany
Department of Radiotherapy, University Hospital Freiburg	Not yet recruiting
Freiburg i. Br., Baden-Wuerttemberg, Germany, 79106
Sub-Investigator: Nicole Wiedenmann, Dr. med.
Sub-Investigator: Marianne Schmucker, Dr. med.
Sub-Investigator: Tanja Schimek-Jasch
Principal Investigator: Anca-Ligia Grosu, Prof. Dr. med.
Principal Investigator: Wolfgang Weber, Prof. Dr. med.

Sponsors and Collaborators

University Hospital Freiburg

Clinical Trials Center Freiburg

University of Freiburg

AG-NUK-RT

Investigators

Study Chair:	Anca-Ligia Grosu, Prof. Dr. med.	Department of Radiotherapy, University Hospital Freiburg
Study Chair:	Wolfgang Weber, Prof. Dr. med.	Department of Nuclear Medicine, University Hospital Freiburg
Study Chair:	Ursula Nestle, PD Dr. med.	Department of Radiotherapy, University Hospital Freiburg

More Information

Publications:

Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010 Sep;96(3):325-7. Epub 2010 Aug 20.

Grosu AL, Weber WA, Franz M, Stärk S, Piert M, Thamm R, Gumprecht H, Schwaiger M, Molls M, Nieder C. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):511-9.

Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):64-74.

Grosu AL, Piert M, Weber WA, Jeremic B, Picchio M, Schratzenstaller U, Zimmermann FB, Schwaiger M, Molls M. Positron emission tomography for radiation treatment planning. Strahlenther Onkol. 2005 Aug;181(8):483-99. Review.

Grosu AL, Lachner R, Wiedenmann N, Stärk S, Thamm R, Kneschaurek P, Schwaiger M, Molls M, Weber WA. Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: first clinical experience. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1450-63.

Grosu AL, Feldmann H, Dick S, Dzewas B, Nieder C, Gumprecht H, Frank A, Schwaiger M, Molls M, Weber WA. Implications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas. Int J Radiat Oncol Biol Phys. 2002 Nov 1;54(3):842-54.

Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, Molls M, Stöcklin G, Schwaiger M. O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study. Eur J Nucl Med. 2000 May;27(5):542-9.

Grosu AL, Weber W, Feldmann HJ, Wuttke B, Bartenstein P, Gross MW, Lumenta C, Schwaiger M, Molls M. First experience with I-123-alpha-methyl-tyrosine spect in the 3-D radiation treatment planning of brain gliomas. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):517-26.

Responsible Party:	Prof. Dr. med. Anca-Ligia Grosu, Department of Radiation Oncology
ClinicalTrials.gov Identifier:	NCT01252459 History of Changes
Other Study ID Numbers:	AG NUK/RT 2010-1
Study First Received:	December 2, 2010
Last Updated:	December 15, 2010
Health Authority:	Germany: Ethics Commission Germany: Federal Office for Radiation Protection

Keywords provided by University Hospital Freiburg:

AA-PET
T1-Gd-MRI
re-irradiation
recurrent glioma

Additional relevant MeSH terms:

Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on June 17, 2013

Amino-acid PET Versus MRI Guided Re-irradiation in Patients With Recurrent Glioblastoma Multiforme (GLIAA)