INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study
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|ClinicalTrials.gov Identifier: NCT02104882|
Recruitment Status : Completed
First Posted : April 7, 2014
Last Update Posted : October 17, 2016
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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)
- 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
- Progression Free Survival [ Time Frame: 3 Years ]
- Overall Survival [ Time Frame: 3 Years ]
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
|Universitätsmedizin Mannheim, University of Heidelberg|
|Mannheim, Germany, 68167|
|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|