Clinical trial NCT02104882: INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study
Official title: INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme
High-Grade Glioma
Malignant Glioma
IORT
Lead sponsor: Universitätsmedizin Mannheim
Sponsor class: OTHER
First posted: 2014-04-07
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 3 Months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 3 Years
measure: Overall Survival
timeFrame: 3 Years
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, University of Heidelberg
Study officials:
affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, University of Heidelberg
name: Frederik Wenz, MD
role: STUDY_CHAIR
affiliation: Department of Neurosurgery, Universitätsmedizin Mannheim, University of Heidelberg
name: Peter Schmiedek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giordano FA, Brehmer S, Abo-Madyan Y, Welzel G, Sperk E, Keller A, Schneider F, Clausen S, Herskind C, Schmiedek P, Wenz F. INTRAGO: intraoperative radiotherapy in glioblastoma multiforme-a phase I/II dose escalation study. BMC Cancer. 2014 Dec 22;14:992. doi: 10.1186/1471-2407-14-992.
citation: Matsutani M, Nakamura O, Nagashima T, Asai A, Fujimaki T, Tanaka H, Nakamura M, Ueki K, Tanaka Y, Matsuda T. Intra-operative radiation therapy for malignant brain tumors: rationale, method, and treatment results of cerebral glioblastomas. Acta Neurochir (Wien). 1994;131(1-2):80-90. doi: 10.1007/BF01401457.
citation: Sakai N, Yamada H, Andoh T, Takada M, Hirata T, Funakoshi T, Doi H, Yanagawa S. [Intraoperative radiation therapy for malignant glioma]. Neurol Med Chir (Tokyo). 1989 Apr;29(4):312-8. doi: 10.2176/nmc.29.312. Japanese.
citation: Fujiwara T, Honma Y, Ogawa T, Irie K, Kuyama H, Nagao S, Takashima H, Hosokawa A, Ohkawa M, Tanabe M. Intraoperative radiotherapy for gliomas. J Neurooncol. 1995;23(1):81-6. doi: 10.1007/BF01058463.
citation: Ortiz de Urbina D, Santos M, Garcia-Berrocal I, Bustos JC, Samblas J, Gutierrez-Diaz JA, Delgado JM, Donckaster G, Calvo FA. Intraoperative radiation therapy in malignant glioma: early clinical results. Neurol Res. 1995 Aug;17(4):289-94. doi: 10.1080/01616412.1995.11740329.