Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme

NCT02685605 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: INTRAGO-IIARO-2016-1AG-NRO-03
• Study Type: interventional
• Target: 314
• Locations: 8 countries
• Sites: 19

Brief Summary

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.

Conditions

Glioblastoma

Keywords

Glioblastoma; Intraoperative Radiotherapy; Radiotherapy Dose Escalation

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival

  Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging

  24 Months

Secondary Outcomes (15)

• Median Overall Survival

  24 Months

• PFS within a 1-2 cm margin around the cavity

  24 Months

• OS with respect to Age

  24 Months

• PFS with respect to Age

  24 Months

• OS with respect to KPS

  24 Months

Study Arms (2)

Experimental Arm (A)

EXPERIMENTAL

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; Radiation: Radiochemotherapy; Drug: Temozolomide

Control Arm (B)

ACTIVE COMPARATOR

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; Drug: Temozolomide

Interventions

Standard surgery PROCEDURE

Control Arm (B); Experimental Arm (A)

Intraoperative radiotherapy RADIATION

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.

Also known as: IORT

Experimental Arm (A)

Radiochemotherapy RADIATION

EBRT to 60 Gy plus 75 mg/m2/d temozolomide

Control Arm (B); Experimental Arm (A)

Temozolomide DRUG

Adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Control Arm (B); Experimental Arm (A)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Multicentric disease (e.g. in both hemispheres) or non-resectable satellite lesions
• Previous cranial radiation therapy
• Cytostatic therapy / chemotherapy for cancer within the past 5 years
• History of cancers or other comorbidities that limit life expectancy to less than five years
• Previous therapy with anti-angiogenic substances (such as bevacizumab)
• Technical impossibility to use MRI or known allergies against MRI and/or CT contrast agents
• Participation in other clinical trials testing cancer-derived investigational agents/procedures.
• Pregnant or breast feeding patients
• Fertile patients refusing to use safe contraceptive methods during the study
• Active egress of fluids from a ventricular defect
• In-field risk organs and/or IORT dose \>8 Gy to any risk organ

Sponsors & Collaborators

• Universitätsmedizin Mannheim: lead
• Carl Zeiss Meditec AG: collaborator
• University of California, Los Angeles: collaborator

Study Sites (19)

Barrow Neurological Institute (SJHMC)

Phoenix, Arizona, 85013, United States

Location

Stritch School of Medicine Loyola University

Maywood, Illinois, 60153, United States

Location

Long Island Jewish Medical Center, North Shore University Hospital

Lake Success, New York, 11042, United States

Location

Lenox Hill Hospital, Hofstra Northwell School of Medicine

New York, New York, 10028, United States

Location

West Virginia University

Morgantown, West Virginia, 26506-9260, United States

Location

Hospital Alemão Oswaldo Cruz

São Paulo, 01323-020, Brazil

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Beijing Tian Tan Hospital, Capital Medical University

Beijing, 100050, China

Location

University Hospital Augsburg

Augsburg, 86156, Germany

Location

Charité - Universitätsmedizin

Berlin, 13353, Germany

Location

St. Georg Hospital

Leipzig, Germany

Location

University Hospital Mannheim

Mannheim, 68167, Germany

Location

Technical University of Munich (TUM), Department of Radiation Oncology

Munich, 81675, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Helios University Hospital Wuppertal

Wuppertal, 42283, Germany

Location

Gangnam Severance Hospital, Yonsei University College of Medicine

Seoul, 06273, South Korea

Location

Catalan Institute of Oncology (ICO)

Barcelona, 08908, Spain

Location

Hospital Reina Sofia

Córdoba, Spain

Location

The London Clinic

London, W1G 6BW, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 25535398 BACKGROUND

• Sarria GR, Sperk E, Han X, Sarria GJ, Wenz F, Brehmer S, Fu B, Min S, Zhang H, Qin S, Qiu X, Hanggi D, Abo-Madyan Y, Martinez D, Cabrera C, Giordano FA. Intraoperative radiotherapy for glioblastoma: an international pooled analysis. Radiother Oncol. 2020 Jan;142:162-167. doi: 10.1016/j.radonc.2019.09.023. Epub 2019 Oct 16.

  PMID: 31629553 BACKGROUND

• Ayala Alvarez DS, Watson PGF, Popovic M, Heng VJ, Evans MDC, Panet-Raymond V, Seuntjens J. Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma. Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):763-773. doi: 10.1016/j.ijrobp.2023.04.031. Epub 2023 May 5.

  PMID: 37150259 BACKGROUND

• Cifarelli CP, Jacobson GM. Intraoperative Radiotherapy in Brain Malignancies: Indications and Outcomes in Primary and Metastatic Brain Tumors. Front Oncol. 2021 Nov 11;11:768168. doi: 10.3389/fonc.2021.768168. eCollection 2021.

  PMID: 34858846 BACKGROUND

• Sarria GR, Smalec Z, Muedder T, Holz JA, Scafa D, Koch D, Garbe S, Schneider M, Hamed M, Vatter H, Herrlinger U, Giordano FA, Schmeel LC. Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. Front Oncol. 2021 Oct 28;11:759873. doi: 10.3389/fonc.2021.759873. eCollection 2021.

  PMID: 34778080 BACKGROUND

• Giordano FA, Brehmer S, Murle B, Welzel G, Sperk E, Keller A, Abo-Madyan Y, Scherzinger E, Clausen S, Schneider F, Herskind C, Glas M, Seiz-Rosenhagen M, Groden C, Hanggi D, Schmiedek P, Emami B, Souhami L, Petrecca K, Wenz F. Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial. Neurosurgery. 2019 Jan 1;84(1):41-49. doi: 10.1093/neuros/nyy018.

  PMID: 29528443 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Chemoradiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Frank A. Giordano, MD

  Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Germany

  PRINCIPAL INVESTIGATOR

• Kevin Petrecca, MD

  Department of Neurosurgery, Montréal Neurological, Institute and Hospital, Montréal, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI (Chair)

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: February 19, 2016
• Study Start: December 9, 2016
• Primary Completion: November 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1); DE (7); CA (1); ES (2); GB (1); US (5); KR (1); CN (1)