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

October 14, 2016 updated by: Frederik Wenz, Universitätsmedizin Mannheim

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Mannheim, Germany, 68167
        • Universitätsmedizin Mannheim, University of Heidelberg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 Months

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: 3 Years
3 Years
Overall Survival
Time Frame: 3 Years
3 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsmedizin Mannheim

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

March 26, 2014

First Submitted That Met QC Criteria

March 31, 2014

First Posted (Estimate)

April 7, 2014

Study Record Updates

Last Update Posted (Estimate)

October 17, 2016

Last Update Submitted That Met QC Criteria

October 14, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INTRAGO-I/II

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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