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NCT Number: NCT02685605

Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Alemão Oswaldo Cruz, São Paulo, Brazil

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Renal Function:

  • Serum Creatinine ≤ 1.5 times ULN

Inclusion criteria

Related to Surgery:

  • IORT must be technically feasible
  • Histology supports diagnosis of GBM

Exclusion criteria

  • 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

Exclusion criteria

Related to Surgery:

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

Treatment and study plan

Standard surgery

Procedure

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.

Other names: IORT

Radiochemotherapy

Radiation

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

Temozolomide

Drug

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

Primary outcomes

  1. Median Progression-Free Survival

    Time frame: 24 Months

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

Secondary outcomes

  1. Median Overall Survival

    Time frame: 24 Months

  2. 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

  3. OS with respect to Age

    Time frame: 24 Months

    Median overall survival of patients <65 vs. ≥ 65 years

  4. 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

  5. OS with respect to KPS

    Time frame: 24 Months

    Median overall survival of patients with KPS 80-100% vs. 60-70%

  6. 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

  7. 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)

  8. 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

  9. 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)

  10. 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)

  11. OS with respect to MGMT promoter methylation status

    Time frame: 24 Months

    OS in patients with promoter methylation vs. no promoter methylation

  12. 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

  13. 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)

  14. 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.

  15. Radiation-related (acute / early delayed / late) neurotoxicity

    Time frame: 24 Months

    Assessed by regular neurological examinations and serial MRI scans

Sponsors and collaborators

Lead sponsor

Universitätsmedizin Mannheim

Other

Collaborators

  • Carl Zeiss Meditec AG
  • University of California, Los Angeles

Registry information

Official study title

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

Acronym: INTRAGO-II

Important dates

Study start
2016
Primary completion
2025
Study completion
2026
First posted
Feb 19, 2016
Registry last updated
Oct 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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