The PROGRAM-study: Awake Mapping Versus Asleep Mapping Versus No Mapping for Glioblastoma Resections

Glioblastoma Clinical Trial

— PROGRAM  

Official title:

The PROGRAM-study: Awake Mapping Versus Asleep Mapping Versus No Mapping for Glioblastoma Resections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04708171
• Other study ID #: MEC-2020-081-2
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: October 1, 2026

Study information

• Verified date: May 2022
• Source: Erasmus Medical Center
• Contact: Jasper Gerritsen, MD
• Phone: +31629119553
• Email: j.gerritsen[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study is designed as an international, multicenter prospective cohort study. Patients with presumed glioblastoma (GBM) in- or near eloquent areas on diagnostic MRI will be selected by neurosurgeons. Patients will be treated following one of three study arms: 1) a craniotomy where the resection boundaries for motor or language functions will be identified by the "awake" mapping technique (awake craniotomy, AC); 2) a craniotomy where the resection boundaries for motor functions will be identified by "asleep" mapping techniques (MEPs, SSEPs, continuous dynamic mapping); 3) a craniotomy where the resection boundaries will not be identified by any mapping technique ("no mapping group"). All patients will receive follow-up according to standard practice.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 453
• Est. completion date: October 1, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Age =18 years and = 90 years

2. Tumor diagnosed as GBM on MRI as assessed by the neurosurgeon

3. Tumors situated in or near eloquent areas; motor cortex, sensory cortex, subcortical pyramidal tract, speech areas or visual areas as indicated on MRI (Sawaya Grading II and II)

4. The tumor is suitable for resection (according to neurosurgeon)

5. Written informed consent

Exclusion Criteria:

1. Tumors of the cerebellum, brain stem or midline

2. Multifocal contrast enhancing lesions

3. Medical reasons precluding MRI (e.g. pacemaker)

4. Inability to give written informed consent (e.g. because of severe language barrier)

5. Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Procedure:
• Awake mapping under local anesthesia
During an awake craniotomy, the patient is awake and cooperative during the resection of the tumor while the surgeon uses electro(sub)cortical mapping to prevent damage to eloquent areas.
• Asleep mapping under general anesthesia
During asleep mapping under general anesthesia, the surgeon uses electro(sub)cortical mapping with evoked potentials (MEPs, SSEPs or continuous dynamic mapping) to prevent damage to eloquent areas.
• Resection under general anesthesia without mapping
During resection under general anesthesia without mapping, the surgeon does not use any intraoperative stimulation mapping techniques to identify eloquent areas.

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven	Vlaams-Brabant
Germany	University Hospital Heidelberg	Heidelberg
Germany	Technical University Munich	Munich
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland
Netherlands	Medical Center Haaglanden	The Hague	Zuid-Holland
Switzerland	Inselspital Universitätsspital Bern	Bern
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California, San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
Erasmus Medical Center	Medical Center Haaglanden, Universitaire Ziekenhuizen Leuven, University of California, San Francisco

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological morbidity	NIHSS deterioration of 1 point or more as compared to baseline value.	Between baseline and 6 weeks/3 months/6 months postoperatively
Primary	Extent of resection	Resection percentage as assessed by an independent neuroradiologist on MRI contrast images with volumetric analysis	Assessed within 72 hours on postoperative MRI scan
Secondary	Progression-free survival	Progression-free survival (PFS) defined as time from diagnosis to disease progression (occurrence of a new tumour lesion with a volume greater than 0.175 cm³, or an increase in residual tumour volume of more than 25%) or death, whichever comes first.	Between surgery and 12 months postoperatively
Secondary	Overall survival	Overall survival (OS) defined as time from diagnosis to death from any cause.	Between surgery and 12 months postoperatively
Secondary	Onco-functional outcome	2D coordinate based on extent of resection (or residual tumor volume) on the x-axis and NIHSS score on the y-axis	Between baseline and 6 weeks/3 months/6 months postoperatively
Secondary	Frequency and severity of Serious Adverse Events (SAEs)	Infections, intracerebral bleeding, epilepsy, aphasia, paresis/paralysis in arms or/and legs (this is not an exhaustive list).	Between surgery and 6 weeks postoperatively
Secondary	Residual tumor volume	Postoperative tumor volume in mm3 as assessed by an independent neuroradiologist on MRI contrast images with volumetric analysis	Assessed within 72 hours on postoperative MRI scan
Secondary	MRC deterioration (for motor gliomas)	MRC deterioration of 1 point or more as compared to baseline value.	Between baseline and 6 weeks/3 months/6 months postoperatively