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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Procedure: Awake mapping under local anesthesia; Procedure: Asleep mapping under general anesthesia; Procedure: Resection under general anesthesia without mapping

• Study Type: Observational
• Enrollment (Anticipated): 453

Contacts and Locations

• Study Contact: Name: Jasper Gerritsen, MD; Phone Number: +31629119553; Email: j.gerritsen@erasmusmc.nl
• Study Contact Backup: Name: Arnaud Vincent, MD PhD; Email: a.vincent@erasmusmc.nl

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Not yet recruiting
      • University Hospitals Leuven
      • Contact: Prof. Steven De Vleeschouwer, MD PhD; Email: steven.devleeschouwer@uzleuven.be
• Germany
  • Heidelberg, Germany
    • Not yet recruiting
    • University Hospital Heidelberg
    • Contact: Christine Jungk, Dr. med.
  • Munich, Germany
    • Not yet recruiting
    • Technical University Munich
    • Contact: Sandro Krieg, Prof. dr. med.; Email: sandro.krieg@tum.de
• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 CE
      • Recruiting
      • Erasmus MC
      • Contact: Jasper Gerritsen, MD; Phone Number: +31629119553; Email: j.gerritsen@erasmusmc.nl
      • Contact: Arnaud Vincent, MD PhD; Phone Number: +31639428949; Email: a.vincent@erasmusmc.nl
    • The Hague, Zuid-Holland, Netherlands, 2261 CP
      • Not yet recruiting
      • Medical Center Haaglanden
      • Contact: Marike Broekman, MD PhD; Phone Number: +31639758253; Email: m.broekman@haaglandenmc.nl
• Switzerland
  • Bern, Switzerland
    • Not yet recruiting
    • INSELSPITAL Universitatsspital Bern
    • Contact: Philippe Schucht, Prof. dr. med.; Email: philippe.schucht@insel.ch
    • Sub-Investigator: Kathleen Seidel, Dr. med.
• United States
  • California
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • University of California, San Francisco
      • Contact: Mitchel Berger, Dr.; Email: mitchel.berger@ucsf.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
      • Not yet recruiting
      • Massachusetts General Hospital
      • Contact: Brian Nahed, Dr.; Email: bnahed@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults with primary or recurrent glioblastoma (GBM).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Awake mapping under local anesthesia	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	Procedure: 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	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological morbidity	NIHSS deterioration of 1 point or more as compared to baseline value.	Between baseline and 6 weeks/3 months/6 months postoperatively
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall survival	Overall survival (OS) defined as time from diagnosis to death from any cause.	Between surgery and 12 months postoperatively
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
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
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
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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Universitaire Ziekenhuizen KU Leuven; University of California, San Francisco; Medical Center Haaglanden
• Investigators: Study Director: Jasper Gerritsen, MD, Erasmus MC

Publications and helpful links

General Publications

• Gerritsen JKW, Zwarthoed RH, Kilgallon JL, Nawabi NL, Jessurun CAC, Versyck G, Pruijn KP, Fisher FL, Lariviere E, Solie L, Mekary RA, Satoer DD, Schouten JW, Bos EM, Kloet A, Nandoe Tewarie R, Smith TR, Dirven CMF, De Vleeschouwer S, Broekman MLD, Vincent AJPE. Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study. Lancet Oncol. 2022 Jun;23(6):802-817. doi: 10.1016/S1470-2045(22)00213-3. Epub 2022 May 12.
• Gerritsen JKW, Dirven CMF, De Vleeschouwer S, Schucht P, Jungk C, Krieg SM, Nahed BV, Berger MS, Broekman MLD, Vincent AJPE. The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study. BMJ Open. 2021 Jul 21;11(7):e047306. doi: 10.1136/bmjopen-2020-047306. Erratum In: BMJ Open. 2022 Aug 8;12(8):e047306corr1.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): October 1, 2025
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: MEC-2020-081-2

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