Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme (INTRAGO-II)

October 10, 2025 updated by: Frank A. Giordano, Universitätsmedizin Mannheim

A Multicenter Randomized Phase III Trial on INTraoperative RAdiotherapy in Newly Diagnosed GliOblastoma Multiforme (INTRAGO II)

INTRAGO II resembles a multicentric, prospective, randomized, 2-arm, open-label clinical phase III trial which tests if the median progression-free survival (PFS) of patients with newly diagnosed glioblastoma multiforme (GBM) can be improved by the addition of intraoperative radiotherapy (IORT) to standard radiochemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
314

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Brazil
      • São Paulo, Brazil, 01323-020
        • Hospital Alemao Oswaldo Cruz
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital
  • China
      • Beijing, China, 100050
        • Beijing Tian Tan Hospital, Capital Medical University
  • Germany
      • Augsburg, Germany, 86156
        • University Hospital Augsburg
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin
      • Leipzig, Germany
        • St. Georg Hospital
      • Mannheim, Germany, 68167
        • University Hospital Mannheim
      • Munich, Germany, 81675
        • Technical University of Munich (TUM), Department of Radiation Oncology
      • Stuttgart, Germany, 70174
        • Klinikum Stuttgart
      • Wuppertal, Germany, 42283
        • Helios University Hospital Wuppertal
  • South Korea
      • Seoul, South Korea, 06273
        • Gangnam Severance Hospital, Yonsei University College of Medicine
  • Spain
      • Barcelona, Spain, 08908
        • Catalan Institute of Oncology (ICO)
      • Córdoba, Spain
        • Hospital Reina Sofia
  • United Kingdom
      • London, United Kingdom, W1G 6BW
        • The London Clinic
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute (SJHMC)
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Stritch School of Medicine Loyola University
    • New York
      • Lake Success, New York, United States, 11042
        • Long Island Jewish Medical Center, North Shore University Hospital
      • New York, New York, United States, 10028
        • Lenox Hill Hospital, Hofstra Northwell School of Medicine
    • West Virginia
      • Morgantown, West Virginia, United States, 26506-9260
        • West Virginia University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Age ≥18 and ≤ 80 years
  2. Karnofsky Performance Score (KPS) ≥ 60%
  3. Supratentorial T1-Gd enhancing lesion(s) amenable to total resection
  4. Legal capacity and ability of subject to understand character and individual consequences of the clinical trial
  5. Patient's written IC obtained at least 24h prior to surgery
  6. For women with childbearing potential: adequate contraception

  7. Patients must have adequate organ functions

    Bone marrow function:

    • Platelets ≥ 75.000/μL
    • WBC ≥ 3.000/μL
    • Hemoglobin ≥ 10.0 g/dL

    Liver Function:

    • ASAT and ALAT ≤ 3.0 times ULN
    • ALP ≤ 2.5 times ULN
    • Total Serum Bilirubin < 1.5 times ULN

    Renal Function:

    • Serum Creatinine ≤ 1.5 times ULN

    Inclusion Criteria Related to Surgery:

  8. IORT must be technically feasible
  9. Histology supports diagnosis of GBM

Exclusion Criteria

  1. Multicentric disease (e.g. in both hemispheres) or non-resectable satellite lesions
  2. Previous cranial radiation therapy
  3. Cytostatic therapy / chemotherapy for cancer within the past 5 years
  4. History of cancers or other comorbidities that limit life expectancy to less than five years
  5. Previous therapy with anti-angiogenic substances (such as bevacizumab)
  6. Technical impossibility to use MRI or known allergies against MRI and/or CT contrast agents
  7. Participation in other clinical trials testing cancer-derived investigational agents/procedures.
  8. Pregnant or breast feeding patients

  9. Fertile patients refusing to use safe contraceptive methods during the study

    Exclusion Criteria Related to Surgery:

  10. Active egress of fluids from a ventricular defect
  11. In-field risk organs and/or IORT dose >8 Gy to any risk organ

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental Arm (A)
Standard surgery plus intraoperative radiotherapy (20-30 Gy) followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).
Procedure: Standard surgery
Radiation: Intraoperative radiotherapy
Dose to applicator surface: 20-30 Gy; Carl Zeiss INTRABEAM System. IORT with a surface dose of 30 Gy is recommended.Should the proximity to any risk structure not allow to apply 30 Gy, a dose reduction by up to 10 Gy (resulting in a surface dose of 20 Gy) is allowed.
Other Names:
  • IORT
Radiation: Radiochemotherapy
EBRT to 60 Gy plus 75 mg/m2/d temozolomide
Drug: Temozolomide
Adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).
Active Comparator: Control Arm (B)
Standard surgery followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).
Procedure: Standard surgery
Radiation: Radiochemotherapy
EBRT to 60 Gy plus 75 mg/m2/d temozolomide
Drug: Temozolomide
Adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Median Progression-Free Survival
Time Frame: 24 Months
Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging
24 Months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Median Overall Survival
Time Frame: 24 Months
24 Months
PFS within a 1-2 cm margin around the cavity
Time Frame: 24 Months
Determined by serial contrast-enhanced MRI scans using modified RANO criteria and serial perfusion imaging
24 Months
OS with respect to Age
Time Frame: 24 Months
Median overall survival of patients <65 vs. ≥ 65 years
24 Months
PFS with respect to Age
Time Frame: 24 Months
Progression-free survival of patients <65 vs. ≥ 65 years; determined according to modified RANO criteria and serial perfusion imaging
24 Months
OS with respect to KPS
Time Frame: 24 Months
Median overall survival of patients with KPS 80-100% vs. 60-70%
24 Months
PFS with respect to KPS
Time Frame: 24 Months
Progression-free survival of patients with KPS 80-100% vs. 60-70%; determined according to modified RANO criteria and serial perfusion imaging
24 Months
OS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin
Time Frame: 24 Months
Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. <0.5 cm)
24 Months
PFS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin
Time Frame: 24 Months
Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. <0.5 cm); determined according to modified RANO criteria and serial perfusion imaging
24 Months
OS with respect to extent of resection
Time Frame: 24 Months

Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. OS will be calculated for the following groups:

  • Max Diameter group 0: 0 cm (no residual tumor)
  • Max Diameter group 1: >0 to ≤1.5 cm (cumulative if multiple residual lesions)
  • Max Diameter group 2: >1.5 cm (cumulative if multiple residual lesions)
24 Months
PFS with respect to extent of resection
Time Frame: 24 Months

Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. PFS will be determined according to modified RANO criteria and serial perfusion imaging for the following groups:

  • Max Diameter group 0: 0 cm (no residual tumor)
  • Max Diameter group 1: >0 to ≤1.5 cm (cumulative if multiple residual lesions)
  • Max Diameter group 2: >1.5 cm (cumulative if multiple residual lesions)
24 Months
OS with respect to MGMT promoter methylation status
Time Frame: 24 Months
OS in patients with promoter methylation vs. no promoter methylation
24 Months
PFS with respect to MGMT promoter methylation status
Time Frame: 24 Months
PFS in patients with promoter methylation vs. no promoter methylation; determined according to modified RANO criteria and serial perfusion imaging
24 Months
Quality of Life (QoL) questionnaire
Time Frame: 24 Months
Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)
24 Months
Activities of daily living (ADL), assessed using the Barthel Index (Mahoney & Barthel, 1965).
Time Frame: 24 Months
Change in functional outcomes as measured by BI from its baseline value.
24 Months
Radiation-related (acute / early delayed / late) neurotoxicity
Time Frame: 24 Months
Assessed by regular neurological examinations and serial MRI scans
24 Months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitätsmedizin Mannheim

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, Los Angeles
Carl Zeiss Meditec AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kevin Petrecca, MD, Department of Neurosurgery, Montréal Neurological, Institute and Hospital, Montréal, Canada
  • Principal Investigator: Frank A. Giordano, MD, Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Germany

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 9, 2016

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2016

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 14, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 10, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INTRAGO-II
  • ARO-2016-1 (Other Identifier: Working Party for Radiation Oncology (ARO) of the DKG)
  • AG-NRO-03 (Other Identifier: German Society for Radiation Oncology (DEGRO))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

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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