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

NCT ID: NCT02104882

Last Updated: 2016-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2016-09-30

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.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: RADIATION

Interventions

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

Intervention Type: RADIATION

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsmedizin Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Frederik Wenz

Director, Department of Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frederik Wenz, MD

Role: STUDY_CHAIR

Department of Radiation Oncology, Universitätsmedizin Mannheim, University of Heidelberg

Peter Schmiedek, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery, Universitätsmedizin Mannheim, University of Heidelberg

Locations

Universitätsmedizin Mannheim, University of Heidelberg

Mannheim, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 25535398 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7709789 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2478913 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7623073 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7477745 (View on PubMed)

Other Identifiers

INTRAGO-I/II

Identifier Type: -

Identifier Source: org_study_id