Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

Not Applicable

Recruiting

• Conditions: Glioblastoma
• Interventions: Radiation: Escalated proton therapy

• Registration Number: NCT05768087
• Lead Sponsor: University of Aarhus

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.

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 Timeline

• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-03-02
• Study First Posted: 2023-03-14
• Study Start: 2024-04-15
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-09
• Primary Completion: 2026-10
• Study Completion: 2029-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

• All eligibility criteria are formulated as inclusion criteria.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Escalated proton therapy	Escalated proton therapy	-

Primary Outcome Measures

Name	Time	Method
Adverse Events	up til 2 years after the end of proton therapy	CTCAE version 5.0
Dose Limiting Toxicities	up til 6 months after the start of proton therapy	CTCAE version 5.0

Trial Locations

Locations (2)

Aarhus University Hospital, Dept. of Oncology; 🇩🇰 Aarhus, Central Denmark Region, Denmark

Danish Centre for Particle Therapy; 🇩🇰 Aarhus, Denmark