Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme

Conditions

Glioblastoma

Keywords

Glioblastoma, Intraoperative Radiotherapy, Radiotherapy Dose Escalation

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.

Palavani LB, de Barros Oliveira L, Reis PA, Batista S, Santana LS, de Freitas Martins LP, Rabelo NN, Bertani R, Welling LC, Figueiredo EG, Paiva WS, Neville IS.

2024-01-154 citations

10.1007/s10143-024-02279-2

NIMG-74. RESPONSE ASSESSMENT AFTER DOSE-ESCALATED RADIOTHERAPY: IMAGING PROTOCOL OF A MULTICENTER PHASE III TRIAL ON INTRAOPERATIVE RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA (INTRAGO-II;ARO2016-1;AG-NRO-03)

Whitney B. Pope, Kevin Petrecca, Alexander Radbruch, Frank A. Giordano, INTRAGO Trialists

Neuro-Oncology2021-11-02

10.1093/neuonc/noab196.571

Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial.

Giordano FA, Brehmer S, Mürle 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, Hänggi D, Schmiedek P, Emami B, Souhami L, Petrecca K, Wenz F.

2019-01-0143 citations

10.1093/neuros/nyy018

NIMG-56. CHARACTERISTIC RESPONSE PATTERNS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA AFTER TREATMENT WITH HIGH SINGLE DOSES OF RADIOTHERAPY

Alex Förster, M. Winkler, Stefanie Brehmer, Marcel Seiz‐Rosenhagen, Daniel Hänggi et al. (8 authors)

Neuro-Oncology2017-11-01

10.1093/neuonc/nox168.630

RTHP-05. INTRAOPERATIVE RADIOTHERAPY (IORT) USING LOW-ENERGY X-RAYS IN A COHORT OF PREDOMINANTLY INCOMPLETELY RESECTED NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (INTRAGO TRIAL)

Frank A. Giordano, Stefanie Brehmer, Bettina Mürle, Grit Welzel, Elena Sperk et al. (17 authors)

Neuro-Oncology2016-11-011 citations

10.1093/neuonc/now212.731

Interventions

PROCEDUREStandard surgery

RADIATIONIntraoperative 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.

RADIATIONRadiochemotherapy

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

DRUGTemozolomide

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Median Progression-Free Survival	24 Months	Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging

Secondary

Measure	Time frame	Description
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
OS with respect to Age	24 Months	Median overall survival of patients \<65 vs. ≥ 65 years
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%
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)
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
Median Overall Survival	24 Months	—
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)
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
Quality of Life (QoL) questionnaire	24 Months	Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)
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.
Radiation-related (acute / early delayed / late) neurotoxicity	24 Months	Assessed by regular neurological examinations and serial MRI scans
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)

Countries

Brazil, Canada, China, Germany, South Korea, Spain, United Kingdom, United States

Outcome results

None listed