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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by University Hospital Freiburg.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborators:
Clinical Trials Center Freiburg
University of Freiburg
AG-NUK-RT
Information provided by:
University Hospital Freiburg
ClinicalTrials.gov Identifier:
NCT01252459
First received: December 2, 2010
Last updated: December 15, 2010
Last verified: December 2010
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

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
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on October 20, 2014