Glioblastoma Radiotherapy Using IMRT or Proton Beams (GRIPS)

Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter. The aim of the GRIPS study is to prospectively test this clinical benefit in a randomized, open-label Phase III study. Patients are treated in the study using either modern photon radiation techniques (standard arm) or proton beams (experimental arm). The primary endpoint is the cumulative toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Proton irradiation; Radiation: Photon irradiation

• Study Type: Interventional
• Enrollment (Estimated): 326
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laila König, Prof. Dr.; Phone Number: 36318 +49 6221 56 36318; Email: studien.radonk@med.uni-heidelberg.de
• Study Contact Backup: Name: Klaus Herfarth, Prof. Dr.; Phone Number: 34091 +49 6221 56 311584; Email: studienkoordination.rad@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany
    • Recruiting
    • Universitatsklinikum Heidelberg
    • Contact: Klaus Herfarth, Prof. Dr.
  • Marburg, Germany
    • Not yet recruiting
    • Universitätsklinikum Gießen und Marburg
    • Contact: Rita Engenhart-Cabillic, Prof. Dr.
  • Stuttgart, Germany
    • Not yet recruiting
    • Klinikum Stuttgart
    • Contact: Marc Münter, Prof. Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• histologically confirmed gliomblastoma WHO IV (operated or after biopsy)
• Indication for radiotherapy / radiochemotherapy
• Informed consent
• KI ≥ 60% or ECOG 0/1
• Age ≥ 18 years
• Sufficient effective contraception

Exclusion Criteria:

• Patient is not able to consent
• Previous radiotherapy in the brain or skull base
• Active medical implants for which there is no ion radiation authorization at the time of treatment (e.g., cardiac pacemaker, defibrillator, ...)
• Contraindication to MRI imaging
• Simultaneous participation in another clinical trial that could influence the outcome of this study or other study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Proton irradiation; Irradiation applied with protons	Radiation: Proton irradiation; proton irradiation applied as follows: 30 x 2 Gy(RBE) 33 x 1,8 Gy (RBE), or 15 x 2,67 Gy (RBE)
Active Comparator: Arm B: Photon IMRT; Photon irradiation applied as intensity-modulated radiotherapy	Radiation: Photon irradiation; proton irradiation applied as follows: 30 x 2 Gy 33 x 1,8 Gy, or 15 x 2,67 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative rate of toxicity	Cumulative rate of toxicity ≥ grade 2 (until progress (max. month 4))	from start of radiotherapy until progress (max. month 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival	1 year and 2 years
Overall survival	Overall survival	1 year and 2 years
Acute Toxicity	according to CTC AE V5.0	start of therapy until 6 weeks after end of therapy (end of therapy up to month 4)
Late Toxicity	according to CTC AE V5.0	6 weeks after end of therapy (end of therapy up to month 4)
Quality of life according to EORTC QLQ-C30	according to EORTC QLQ-C30	1 year and 2 years
Quality of life according to EORTC QLQ-BN20	according to EORTC QLQ-BN20	1 year and 2 years
Neurocognition	according to Hopkins Verbal Learning Test-Revised	1 year and 2 years
Measuring number of Lymphocytes count		end of therapy up to month 4

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Principal Investigator: Laila König, Prof. Dr., University Hospital of Heidelberg, Radiation Oncology

Publications and helpful links

General Publications

• Konig L, Jakel C, von Knebel Doeberitz N, Kieser M, Eberle F, Munter M, Debus J, Herfarth K. Glioblastoma radiotherapy using Intensity modulated Radiotherapy (IMRT) or proton Radiotherapy-GRIPS Trial (Glioblastoma Radiotherapy via IMRT or Proton BeamS): a study protocol for a multicenter, prospective, open-label, randomized, two-arm, phase III study. Radiat Oncol. 2021 Dec 20;16(1):240. doi: 10.1186/s13014-021-01962-8.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Estimated): September 19, 2030
• Study Completion (Estimated): January 19, 2033

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: GRIPS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No