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

Glioblastoma Multiforme Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02104882
• Other study ID #: INTRAGO-I/II
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 26, 2014
• Last updated: October 14, 2016
• Start date: March 2014
• Est. completion date: September 2016

Study information

• Verified date: October 2016
• Source: Universitätsmedizin Mannheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Office for Radiation Protection
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

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

Locations

Country	Name	City	State
Germany	Universitätsmedizin Mannheim, University of Heidelberg	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsmedizin Mannheim

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View Citation

Giordano FA, Abo-Madyan Y, Brehmer S, Herskind C, Sperk E, Schneider F, Clausen S, Welzel G, Schmiedek P, Wenz F. Intraoperative radiotherapy (IORT)—a resurrected option for treating glioblastoma? Transl Cancer Res 2014 Jan 14. doi: 10.3978/j.issn.2218-676X.2014.01.03

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. — View 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. — View 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. Japanese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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	3 Months	Yes
Secondary	Progression Free Survival		3 Years	No
Secondary	Overall Survival		3 Years	No