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

Universitätsmedizin Mannheim

Status and phase: Completed; Phase 2; Phase 1

Conditions: Glioblastoma Multiforme

Treatments: Radiation: Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)

Study type: Interventional

Funder types: Other

Identifiers

NCT02104882

INTRAGO-I/II

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Intraoperative Radiotherapy

Experimental group

Description:

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.

Treatment:

Radiation: Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)