Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05768087
• Other study ID #: 1-10-72-190-22
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2024
• Est. completion date: May 2029

Study information

• Verified date: May 2024
• Source: University of Aarhus
• Contact: Birgit K Bach
• Phone: +4529797231
• Email: dcpt_kfe[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: May 2029
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Dept. of Oncology	Aarhus	Central Denmark Region
Denmark	Danish Centre for Particle Therapy	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Danish Cancer Society

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	CTCAE version 5.0	up til 2 years after the end of proton therapy
Primary	Dose Limiting Toxicities	CTCAE version 5.0	up til 6 months after the start of proton therapy