Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma

Not Applicable

Suspended

• Conditions: Glioblastoma
• Interventions: Radiation: gamma knife radiosurgery (15 Gy to 50% isodose)

• Registration Number: NCT03055208
• Lead Sponsor: Universitätsmedizin Mannheim

Brief Summary

Gamma GBM is a single-arm phase II trial that prospectively measures the progression-free survival time after addition of an early gamma knife boost to areas of residual tumor to standard-of-care (surgery, chemo-radiotherapy, chemotherapy).

Detailed Description

Glioblastomas are highly malignant brain tumors that recur about 6 months after treatment. Most recurrences develop at the edge of the surgical margin and a common reason for an early recurrence of a glioblastoma is when tumors are not completely resected. This may be the case when intraoperative neuro-monitoring indicates that further resection would impair certain motor functions. Physicians can identify residual tumor in early (24-72h after surgery) postoperative MRI scans and could treat these regions. However, this treatment would not be a part of the recommended standard of care and thus, any further treatment of this areas will need a clinical trial.

The aim of this trial is to evaluate if the use of another modality to deplete these areas of residual tumor identified in early postoperative MRI scans will provide a relevant benefit in terms of progression-free survival (which means a prolongation of the time that patients do not experience a re-growth of the tumor). The modality is termed "radiosurgery", which is a non-invasive technique to delete cells without using a blade but a highly focused beam of gamma rays.

The machine that focusses these rays (like a magnifying glass that can focus light), is called 'gamma knife'. Gamma knife radiosurgery is a safe and effective treatment for a plethora of malignant and benign brain tumors and the technique is used since the 1950s and there has been a continuous improvement of precision and patient comfort up to now.

Study Timeline

• Study Start: 2017-02-08
• Study First Submitted: 2017-02-09
• Study First Submitted QC: 2017-02-13
• Study First Posted: 2017-02-16
• Primary Completion: 2020-03-30
• Status Verified: 2023-05
• Study Completion: 2023-05-09
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-05-11

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Age ≥ 18
• Karnofsky performance status score ≥ 60
• histology must be glioblastoma (frozen sections during surgery)
• radiographic proof of residual tumor
• Informed consent
• adequate birth control (e.g., oral contraceptives)

Exclusion Criteria

• any previous cranial radiotherapy
• histology inconclusive or low(er)-grade astrocytoma
• contraindications for chemo- or radiotherapy
• bleeding or clotting disorders
• contraindications for MRI or CT scans

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiosurgery	gamma knife radiosurgery (15 Gy to 50% isodose)	Following intraoperative confirmation of glioblastoma (frozen section): Early (24-72h post surgery) stereotactic ablation (gamma knife radiosurgery) of residual tumor (defined in early postoperative T1-weighted MRI scanning with and without contrast), followed by standard-of-care therapy (chemo-radiotherapy with 60 Gy external beam radiation therapy (EBRT) and 75 mg/m2/d temozolomide, followed by adjuvant chemotherapy with 150-200 mg/m2/d/cycle temozolomide in a 5/28 days schedule).

Primary Outcome Measures

Name	Time	Method
Median Progression-Free Survival Time (PFS)	2 years	PFS is defined as the time span of initial diagnosis (i.e., the day of surgery) until tumor progression is confirmed in follow-up MRI scans. All scans will be assessed using modified Response Assessment in Neuro-Oncology (RANO) criteria or until death by any cause.

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival Time (OS)	2 years	OS is defined as the time span of initial diagnosis (i.e., the day of surgery) until death by any cause.
Radiation-related (acute / early delayed / late) neurotoxicity	2 years	Assessed by regular neurological examinations
Incidence of symptomatic radionecrosis	2 years	Assessed by serial MRI scans

Trial Locations

Locations (1)

Department of Radiotherapy University Hospital Mannheim; 🇩🇪 Mannheim, Germany