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Glioblastoma MultiformePhase 1/2NCT02104882

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

A Phase 1/2 study testing Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy) in people with Glioblastoma Multiforme, run by Universitätsmedizin Mannheim at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Glioblastoma Multiforme
What is being tested?
Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteGermany
Study dates
Mar 2014to Sep 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed glioblastoma multiforme in frozen sections
  • Age ≥50 years
  • Karnofsky Performance Index ≥ 50%
  • Informed consent
  • Adequate birth control (e.g., oral contraceptives)

Who cannot join

  • 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.
Show all 10Show fewer
  • Contraindications for general anaesthesia
  • Bleeding or clotting disorders
  • Contraindications for MRI or CT scans
  • Pregnant or breastfeeding women

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsmedizin Mannheim, University of Heidelberg

    Mannheim, 68167

Other trials in Germany

About this study

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).

Read more

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.

Being tested
Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)
Keywords
Glioblastoma Multiforme, High-Grade Glioma, Malignant Glioma, IORT
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT02104882
Study groupRoleWhat they receive
Intraoperative RadiotherapyExperimentalFollowing 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.
Receives: Radiation: Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3 Months

Secondary outcomes (2)

  1. Progression Free Survival

    Measured: 3 Years

  2. Overall Survival

    Measured: 3 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionSep 2016
  4. Study completionSep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02104882
Sponsor's protocol ID
INTRAGO-I/II
Status last verified
Oct 2016
First submitted
26 Mar 2014
Last updated
17 Oct 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 25535398

  • 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.

    PubMed 7709789

  • 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.

    PubMed 2478913

  • 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.

    PubMed 7623073

  • 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.

    PubMed 7477745

  • Stein A, Bridgewater J, Klumpen HJ, Gruenberger T, Shannon J, Fornaro L, Jensen LH, Arnold D, Primrose J, Goldstein D, Lohse AW, Wilmink J, Pession U, Modest DP, Kasper S, Wasan HS, Palmer D, de Vos-Geelen J, Folprecht G, Mohl A, Pepic A, Vettorazzi E, Wege H; ACTICCA-1 Investigators. Adjuvant chemotherapy with cisplatin and gemcitabine compared to standard of care after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1/AIO-HEP-0112 trial). Ann Oncol. 2026 Oct 24:S0923-7534(26)08068-3. doi: 10.1016/j.annonc.2026.10.1278. Online ahead of print.

    PubMed 42926109

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intraoperative Radiotherapy (Applicator Surface Dose: 20-40 Gy) in people with Glioblastoma Multiforme, run by Universitätsmedizin Mannheim at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 3 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02104882, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2016.

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