Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme (INTRAGO-II)

Universitätsmedizin Mannheim

Status and phase: Active, not recruiting; Phase 3

Conditions: Glioblastoma

Treatments: Procedure: Standard surgery; Drug: Temozolomide; Radiation: Intraoperative radiotherapy; Radiation: Radiochemotherapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02685605

ARO-2016-1 (Other Identifier)

INTRAGO-II

AG-NRO-03 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 314 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

   Exclusion Criteria Related to Surgery:

10. Active egress of fluids from a ventricular defect

11. In-field risk organs and/or IORT dose >8 Gy to any risk organ

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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314 participants in 2 patient groups

Experimental Arm (A)

Experimental group

Description:

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).

Treatment:

Radiation: Radiochemotherapy

Radiation: Intraoperative radiotherapy

Drug: Temozolomide

Procedure: Standard surgery

Control Arm (B)

Active Comparator group

Description:

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).

Treatment:

Radiation: Radiochemotherapy

Drug: Temozolomide

Procedure: Standard surgery