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| ID | Type | Description | Link |
|---|---|---|---|
| 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) |
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| Name | Class |
|---|---|
| Carl Zeiss Meditec AG | INDUSTRY |
| University of California, Los Angeles | OTHER |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard surgery | Procedure |
| ||
| Intraoperative radiotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Median Progression-Free Survival | Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging | 24 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Median Overall Survival | 24 Months | |
| PFS within a 1-2 cm margin around the cavity | Determined by serial contrast-enhanced MRI scans using modified RANO criteria and serial perfusion imaging | 24 Months |
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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:
Liver Function:
Renal Function:
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
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute (SJHMC) | Phoenix | Arizona | 85013 | United States | ||
| Stritch School of Medicine Loyola University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25535398 | Background | 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. | |
| 31629553 | Background |
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| 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. |
|
|
| 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). |
|
| OS with respect to Age | Median overall survival of patients <65 vs. ≥ 65 years | 24 Months |
| PFS with respect to Age | 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 | Median overall survival of patients with KPS 80-100% vs. 60-70% | 24 Months |
| PFS with respect to KPS | 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 | 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 | 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 | 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:
| 24 Months |
| PFS with respect to extent of resection | 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:
| 24 Months |
| OS with respect to MGMT promoter methylation status | OS in patients with promoter methylation vs. no promoter methylation | 24 Months |
| PFS with respect to MGMT promoter methylation status | 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 | 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). | Change in functional outcomes as measured by BI from its baseline value. | 24 Months |
| Radiation-related (acute / early delayed / late) neurotoxicity | Assessed by regular neurological examinations and serial MRI scans | 24 Months |
| Maywood |
| Illinois |
| 60153 |
| United States |
| Long Island Jewish Medical Center, North Shore University Hospital | Lake Success | New York | 11042 | United States |
| Lenox Hill Hospital, Hofstra Northwell School of Medicine | New York | New York | 10028 | United States |
| West Virginia University | Morgantown | West Virginia | 26506-9260 | United States |
| Hospital Alemão Oswaldo Cruz | São Paulo | 01323-020 | Brazil |
| Montreal Neurological Institute and Hospital | Montreal | Quebec | H3A 2B4 | Canada |
| Beijing Tian Tan Hospital, Capital Medical University | Beijing | 100050 | China |
| University Hospital Augsburg | Augsburg | 86156 | Germany |
| Charité - Universitätsmedizin | Berlin | 13353 | Germany |
| St. Georg Hospital | Leipzig | Germany |
| University Hospital Mannheim | Mannheim | 68167 | Germany |
| Technical University of Munich (TUM), Department of Radiation Oncology | Munich | 81675 | Germany |
| Klinikum Stuttgart | Stuttgart | 70174 | Germany |
| Helios University Hospital Wuppertal | Wuppertal | 42283 | Germany |
| Gangnam Severance Hospital, Yonsei University College of Medicine | Seoul | 06273 | South Korea |
| Catalan Institute of Oncology (ICO) | Barcelona | 08908 | Spain |
| Hospital Reina Sofia | Córdoba | Spain |
| The London Clinic | London | W1G 6BW | United Kingdom |
| 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. |
| 37150259 | 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. |
| 34858846 | 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. |
| 34778080 | 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. |
| 42372746 | Derived | Giordano FA, Ganslandt O, Munter MW, Combs SE, Diehl C, Meyer B, Herrlinger U, Schneider M, Kahl KH, Shiban E, Goenka A, Schulder M, Lucas A, Plans G, Brehmer S, Ruder AM, Garcia-Cabezas S, Solivera J, Cifarelli CP, Wenz F, Sarria GR, Pope WB, Layer JP, Tsien CI, Petrecca K; INTRAGO-II Study Group. Dose escalation with intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO-II): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Jul;27(7):864-878. doi: 10.1016/S1470-2045(26)00235-4. |
| 29528443 | Derived | 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. |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D059248 | Chemoradiotherapy |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D011878 | Radiotherapy |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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