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INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02104882
Recruitment Status : Completed
First Posted : April 7, 2014
Last Update Posted : October 17, 2016
Sponsor:
Information provided by (Responsible Party):
Frederik Wenz, Universitätsmedizin Mannheim

Study Description
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Brief Summary:

Glioblastoma multiforme (GBM) is a disease with an extremely poor prognosis. Despite surgery and radiochemotherapy, the tumors are likely to grow back very quickly.

Intraoperative radiotherapy (IORT) may improve local control rates while sparing healthy tissue (Giordano et al. 2014). IORT takes place before cranioplasty directly after gross (or subtotal) tumor resection. Several past studies on IORT for GBM conducted in Japan and Spain have yielded encouraging results (Sakai et al. 1989; Matsutani et al. 1994; Fujiwara et al. 1995; Ortiz de Urbina et al. 1995).

However, the full potential of the procedure is to date largely unexplored as most previous studies used forward-scattering (electron-based) irradiation techniques, which frequently led to inadequately covered target volumes. With the advent of the spherically irradiation devices such as the Intrabeam® system (Carl Zeiss Meditec AG, Oberkochen, Germany), even complex cavities can be adequately covered with irradiation during IORT. However, there is no data on the maximum tolerated dose of IORT with low-energy X-rays as generated by this system.

The INTRAGO I/II study aims to find out which dose of a single shot of radiation, delivered intraoperatively direct after surgery, is tolerable for patients with GBM. A secondary goal of the study is to find out whether the procedure may improve survival rates.


Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Radiation: Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study
Study Start Date : March 2014
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Intraoperative Radiotherapy
Following conventional frameless neuronavigation-guided microsurgical tumor resection, patients will receive IORT with 20-40 Gy (prescribed to the applicator surface). Not later than 4 weeks, radiochemotherapy (RCT) will be initiated, consisting of a total EBRT dose of 60 Gy (delivered in fractions of 2 Gy) and concomitant chemotherapy with temozolomide (50 mg/m2/d). Four weeks after RCT, cycling chemotherapy with temozolomide (150-200mg/m2/d/cycle) will be applied.
 Radiation: Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)


Outcome Measures
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Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 3 Months ]

    The maximum tolerated (single) dose of IORT with 50 kV X-rays will be assessed using a classical "3+3" design:

    The first cohort of 3 patients will receive IORT with 20 Gy (prescribed to the applicator surface). If none of these patients experiences a DLT, another three patients will be treated at the next higher dose level (30 Gy). However, should a patient experience a DLT, 3 more patients will be treated at the same dose level. The dose escalation stops if two ore more patients in a cohort of 3-6 patients experience DLT. The MTD is then defined as the dose level just below the toxic dose level.

    Two types of DLT are defined:

    Early DLT (≤ 3 weeks after IORT):

    • wound infections / wound healing difficulties requiring surgical intervention
    • IORT-related cerebral bleeding or ischemia

    Delayed DLT (≤ 3 months after IORT):

    • Symptomatic brain necrosis requiring surgical intervention
    • Early termination of EBRT (before the envisaged dose of 60 Gy) due to radiotoxicity


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 3 Years ]
  2. Overall Survival [ Time Frame: 3 Years ]

Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed glioblastoma multiforme in frozen sections
  • Age ≥50 years
  • Karnofsky Performance Index ≥ 50%
  • Informed consent
  • Adequate birth control (e.g., oral contraceptives)

Exclusion Criteria:

  • Astrocytoma ≤ WHO grade III
  • Gliomatosis cerebri
  • Multifocal lesions
  • Infratentorial localization
  • Previous cranial radiation therapy (any location)
  • Uncontrolled intercurrent illnesses including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Contraindications for general anaesthesia
  • Bleeding or clotting disorders
  • Contraindications for MRI or CT scans
  • Pregnant or breastfeeding women
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02104882


Locations
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Germany
Universitätsmedizin Mannheim, University of Heidelberg
Mannheim, Germany, 68167
Sponsors and Collaborators
Universitätsmedizin Mannheim
Investigators
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Study Chair: Frederik Wenz, MD Department of Radiation Oncology, Universitätsmedizin Mannheim, University of Heidelberg
Principal Investigator: Peter Schmiedek, MD Department of Neurosurgery, Universitätsmedizin Mannheim, University of Heidelberg
More Information
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Publications:

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Responsible Party: Frederik Wenz, Director, Department of Radiation Oncology, Universitätsmedizin Mannheim
ClinicalTrials.gov Identifier: NCT02104882    
Other Study ID Numbers: INTRAGO-I/II
First Posted: April 7, 2014    Key Record Dates
Last Update Posted: October 17, 2016
Last Verified: October 2016
Keywords provided by Frederik Wenz, Universitätsmedizin Mannheim:
Glioblastoma Multiforme
High-Grade Glioma
Malignant Glioma
IORT
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue