Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

• Sponsor: University of Aarhus (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05768087
• Collaborator: Danish Cancer Society (Other)
• Enrollment: 36
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 72
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Radiation: Escalated proton therapy	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients - A Phase 1 Proton Dose Finding Trial -
• Anticipated Study Start Date: May 1, 2023
• Anticipated Primary Completion Date: Oct 1, 2026
• Anticipated Study Completion Date: May 1, 2029

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Adverse Events [up til 2 years after the end of proton therapy]

   CTCAE version 5.0

2. Dose Limiting Toxicities [up til 6 months after the start of proton therapy]

   CTCAE version 5.0

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Danish Center for Particle Therapy	Aarhus		Denmark	8200

Sponsors and Collaborators

• University of Aarhus
• Danish Cancer Society

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT05768087
• Other Study ID Numbers: 1-10-72-190-22
• First Posted: Mar 14, 2023
• Last Update Posted: Mar 14, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioblastoma

Study Results

No Results Posted as of Mar 14, 2023