Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme
- Conditions
- Glioblastoma
- Interventions
- Procedure: Standard surgeryRadiation: Intraoperative radiotherapyRadiation: Radiochemotherapy
- Registration Number
- NCT02685605
- Lead Sponsor
- Universitätsmedizin Mannheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 314
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm (A) Standard surgery 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). Experimental Arm (A) Intraoperative radiotherapy 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). Experimental Arm (A) Temozolomide 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). Control Arm (B) Standard surgery 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). Experimental Arm (A) Radiochemotherapy 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). Control Arm (B) Radiochemotherapy 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). Control Arm (B) Temozolomide 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).
- Primary Outcome Measures
Name Time Method Median Progression-Free Survival 24 Months Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging
- Secondary Outcome Measures
Name Time Method Median Overall Survival 24 Months OS with respect to Age 24 Months Median overall survival of patients \<65 vs. ≥ 65 years
PFS within a 1-2 cm margin around the cavity 24 Months Determined by serial contrast-enhanced MRI scans using modified RANO criteria and serial perfusion imaging
PFS with respect to KPS 24 Months Progression-free survival of patients with KPS 80-100% vs. 60-70%; determined according to modified RANO criteria and serial perfusion imaging
OS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin 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)
OS with respect to extent of resection 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)Activities of daily living (ADL), assessed using the Barthel Index (Mahoney & Barthel, 1965). 24 Months Change in functional outcomes as measured by BI from its baseline value.
PFS with respect to Age 24 Months Progression-free survival of patients \<65 vs. ≥ 65 years; determined according to modified RANO criteria and serial perfusion imaging
OS with respect to KPS 24 Months Median overall survival of patients with KPS 80-100% vs. 60-70%
Quality of Life (QoL) questionnaire 24 Months Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)
Radiation-related (acute / early delayed / late) neurotoxicity 24 Months Assessed by regular neurological examinations and serial MRI scans
PFS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin 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
OS with respect to MGMT promoter methylation status 24 Months OS in patients with promoter methylation vs. no promoter methylation
PFS with respect to MGMT promoter methylation status 24 Months PFS in patients with promoter methylation vs. no promoter methylation; determined according to modified RANO criteria and serial perfusion imaging
PFS with respect to extent of resection 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)
Trial Locations
- Locations (19)
Beijing Tian Tan Hospital, Capital Medical University
🇨🇳Beijing, China
Charité - Universitätsmedizin
🇩🇪Berlin, Germany
St. Georg Hospital
🇩🇪Leipzig, Germany
University Hospital Mannheim
🇩🇪Mannheim, Germany
Gangnam Severance Hospital, Yonsei University College of Medicine
🇰🇷Seoul, Korea, Republic of
Helios University Hospital Wuppertal
🇩🇪Wuppertal, Germany
Catalan Institute of Oncology (ICO)
🇪🇸Barcelona, Spain
Klinikum Stuttgart
🇩🇪Stuttgart, Germany
The London Clinic
🇬🇧London, United Kingdom
Hospital Reina Sofia
🇪🇸Córdoba, Spain
Barrow Neurological Institute (SJHMC)
🇺🇸Phoenix, Arizona, United States
Stritch School of Medicine Loyola University
🇺🇸Maywood, Illinois, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Long Island Jewish Medical Center, North Shore University Hospital
🇺🇸Lake Success, New York, United States
Lenox Hill Hospital, Hofstra Northwell School of Medicine
🇺🇸New York, New York, United States
Hospital Alemão Oswaldo Cruz
🇧🇷São Paulo, Brazil
University Hospital Augsburg
🇩🇪Augsburg, Germany
Technical University of Munich (TUM), Department of Radiation Oncology
🇩🇪Munich, Germany
Montreal Neurological Institute and Hospital
🇨🇦Montréal, Quebec, Canada