Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

May 8, 2024 updated by: University of Aarhus

Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients - A Phase 1 Proton Dose Finding Trial -

The goal of this phase 1 dose finding study is to to assess the clinical tolerability and safety of escalated dose proton therapy in glioblastoma patients treated with multimodality treatment, according to treatment volume.

The main questions it aims to answer are:

  • what is the maximum tolerated proton dose in glioblastoma patients?
  • is the maximum tolerated proton dose in glioblastoma patients dependent on treatment volume?
  • what is the recommended phase 2 proton dose in glioblastoma patients?

Patients will be asked to undergo radiotherapy to step-wise escalated doses using proton therapy as part of their multimodality treatment. Patients will be monitored closely for treatment effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, single-arm, phase 1 proton dose finding trial, aiming to assess the clinical tolerability and safety of escalated dose proton therapy (PT) in glioblastoma (GBM) patients, according to treatment volume. Radiotherapy will be administered with protons for the entire treatment, escalating the proton fraction-dose with the overall treatment time unchanged. The escalated proton dose will be prescribed to a subvolume of the radiation target. Escalated PT will be employed within the multimodality treatment; surgical procedures and concomitant and adjuvant chemotherapy follow the standard-of-care.

Patients will be subdivided in two groups based on the volume of the radiation target: patients with a CTV2 volume of <200 cc will be placed in group 1 and those with a volume ≥ 200 cc in group 2. Per group, proton dose will be escalated stepwise, which will be guided by a time to event continuous reassessment method (TiTE-CRM) to identify the MTD in this specific combination treatment.

The MTD in this trial is defined as the highest proton dose level at which no more than 30% of the patients develop dose limiting toxicities (DLTs) assessed up to 6 months after the start of PT.

Patient accrual to the main (dose escalation) part of the study ends when the MTD has been identified. If the statistically recommended MTD is declared, an expansion cohort to a total of 6 patients treated at the MTD and 6 patients at the MTD-1 (i.e. 1 dose level below MTD) will be considered. When all patients have been followed for toxicity for at least 1 year after the end of PT (and to a maximum of 2 years), the recommended phase 2 dose (RP2D) will be determined based on the full toxicity profile.

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
      • Aarhus, Denmark, 8200
        • Recruiting
        • Danish Centre for Particle Therapy
        • Contact:
        • Principal Investigator:
          • Anouk K Trip, MD PhD
    • Central Denmark Region
      • Aarhus, Central Denmark Region, Denmark, 8200
        • Recruiting
        • Aarhus University Hospital, Dept. of Oncology
        • Contact:
          • Anne Helland Christiansen
        • Principal Investigator:
          • Slavka Lukacova, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (main):

  • Newly diagnosed, contrast-enhancing GBM, IDHwt (WHO 2021 classification).
  • Maximal safe surgical resection is required; any extent of surgical resection is allowed (including biopsy-only).
  • Patient with target volume and location eligible for 60 Gy chemoradiotherapy.
  • Minimum distance between GTV and critical OAR (brainstem, chiasm, optic nerves and tracts in case of serviceable vision) of 5 mm on MRI-scan.
  • Age ≥ 18 years.
  • Karnofsky Performance Status grade of ≥ 70.
  • Adequate blood counts as assessed by treating physician.
  • Absence of any contraindication to undergo MRI and/or to receive Gadolinium contrast agent.
  • Before patient registration, written informed consent must be given according to Good Clinical Practice, and national/local regulations.

Exclusion Criteria:

  • All eligibility criteria are formulated as inclusion criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Escalated proton therapy
Radiation: Escalated proton therapy
According to allocated dose level: level 1-8, 69-90 Gy in 30 fractions of 2.3-3.0 Gy, to a subvolume of the radiation target

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: up til 2 years after the end of proton therapy
CTCAE version 5.0
up til 2 years after the end of proton therapy
Dose Limiting Toxicities
Time Frame: up til 6 months after the start of proton therapy
CTCAE version 5.0
up til 6 months after the start of proton therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

Danish Cancer Society

Investigators

  • Principal Investigator: Anouk K Trip, MD PhD, Danish Centre for Particle Therapy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2024

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

March 2, 2023

First Submitted That Met QC Criteria

March 2, 2023

First Posted (Actual)

March 14, 2023

Study Record Updates

Last Update Posted (Actual)

May 9, 2024

Last Update Submitted That Met QC Criteria

May 8, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1-10-72-190-22

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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