Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM)

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).

Study Overview

• Status: Suspended
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: gamma knife radiosurgery (15 Gy to 50% isodose)

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • Department of Radiotherapy University Hospital Mannheim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiosurgery; 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).

Radiation: gamma knife radiosurgery (15 Gy to 50% isodose); Radiosurgery with a gamma knife resembles the application of a precisely focused, high single dose of ionizing irradiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-Free Survival Time (PFS)	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.	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Universitätsmedizin Mannheim
• Investigators: Principal Investigator: Frank A Giordano, MD, University Medical Center Mannheim

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2017
• Primary Completion (Actual): March 30, 2020
• Study Completion (Anticipated): May 9, 2023

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 13, 2017
• First Posted (Actual): February 16, 2017

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Glioblastoma; Radiosurgery; Gamma Knife
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Glioblastoma; Neoplasm, Residual
• Other Study ID Numbers: Gamma-GBM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No