Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

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: Glioblastoma
• Intervention / Treatment: Radiation: Escalated proton therapy

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

• Study Contact: Name: Birgit K Bach; Phone Number: +4529797231; Email: dcpt_kfe@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Danish Centre for Particle Therapy
    • Contact: Birgit K Bach; Phone Number: +4529797231; Email: dcpt_kfe@rm.dk
    • 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

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

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: 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	CTCAE version 5.0	up til 2 years after the end of proton therapy
Dose Limiting Toxicities	CTCAE version 5.0	up til 6 months after the start of proton therapy

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Danish Cancer Society
• Investigators: Principal Investigator: Anouk K Trip, MD PhD, Danish Centre for Particle Therapy

Study record dates

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: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• 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