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

NCT ID: NCT01252459

Last Updated: 2010-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2014-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Recurrent Glioma (Glioblastoma Multiforme)

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: AA-PET based target volume delineation

Experimental intervention (Arm A): High-precision re-irradiation. Target volume delineation based on AA-PET.

Group Type EXPERIMENTAL

Radiation Therapy

Intervention Type RADIATION

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

Arm B: T1Gd-MRI based target volume delineation

Control intervention (Arm B): High-precision re-irradiation. Target volume delineation based on T1Gd-MRI.

Group Type ACTIVE_COMPARATOR

Radiation Therapy

Intervention Type RADIATION

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

Interventions

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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

Intervention Type 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

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Clinical Trials Center Freiburg

UNKNOWN

Sponsor Role collaborator

University of Freiburg

OTHER

Sponsor Role collaborator

AG-NUK-RT

UNKNOWN

Sponsor Role collaborator

University Hospital Freiburg

OTHER

Sponsor Role lead

Responsible Party

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Department of Radiation Oncology

Principal Investigators

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Anca-Ligia Grosu, Prof. Dr. med.

Role: STUDY_CHAIR

Department of Radiotherapy, University Hospital Freiburg

Wolfgang Weber, Prof. Dr. med.

Role: STUDY_CHAIR

Department of Nuclear Medicine, University Hospital Freiburg

Ursula Nestle, PD Dr. med.

Role: STUDY_CHAIR

Department of Radiotherapy, University Hospital Freiburg

Locations

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Department of Radiotherapy, University Hospital Freiburg

Freiburg I. Br., Baden-Wurttemberg, Germany

Site Status

Countries

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Germany

Central Contacts

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Anca-Ligia Grosu, Prof. Dr. med.

Role: CONTACT

Phone: 0049-761-270

Email: [email protected]

Ursula Nestle, PD Dr. med.

Role: CONTACT

Phone: 0049-761-270

Email: [email protected]

References

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Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010 Sep;96(3):325-7. doi: 10.1016/j.radonc.2010.08.001. Epub 2010 Aug 20.

Reference Type BACKGROUND
PMID: 20728952 (View on PubMed)

Grosu AL, Weber WA, Franz M, Stark 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. doi: 10.1016/j.ijrobp.2005.01.056.

Reference Type BACKGROUND
PMID: 16168843 (View on PubMed)

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. doi: 10.1016/j.ijrobp.2005.01.045.

Reference Type BACKGROUND
PMID: 16111573 (View on PubMed)

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. doi: 10.1007/s00066-005-1422-7.

Reference Type BACKGROUND
PMID: 16044216 (View on PubMed)

Grosu AL, Lachner R, Wiedenmann N, Stark 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. doi: 10.1016/s0360-3016(03)00279-7.

Reference Type BACKGROUND
PMID: 12873691 (View on PubMed)

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. doi: 10.1016/s0360-3016(02)02984-x.

Reference Type BACKGROUND
PMID: 12377338 (View on PubMed)

Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, Molls M, Stocklin 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. doi: 10.1007/s002590050541.

Reference Type BACKGROUND
PMID: 10853810 (View on PubMed)

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. doi: 10.1016/s0360-3016(00)00423-5.

Reference Type BACKGROUND
PMID: 10802381 (View on PubMed)

Oehlke O, Mix M, Graf E, Schimek-Jasch T, Nestle U, Gotz I, Schneider-Fuchs S, Weyerbrock A, Mader I, Baumert BG, Short SC, Meyer PT, Weber WA, Grosu AL. Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) - protocol of a randomized phase II trial (NOA 10/ARO 2013-1). BMC Cancer. 2016 Oct 5;16(1):769. doi: 10.1186/s12885-016-2806-z.

Reference Type DERIVED
PMID: 27716184 (View on PubMed)

Other Identifiers

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AG NUK/RT 2010-1

Identifier Type: -

Identifier Source: org_study_id