Escalated Dose Proton Therapy Within the Multimodality Treatment of Glioblastoma Patients

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05768087
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Aarhus
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Anouk K Trip, MD PhD
Principal Investigator Affiliation	Danish Center for Particle Therapy
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	Denmark
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma

Additional Details

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.

Arms & Interventions

Arms

Experimental: Escalated proton therapy

Interventions

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

Contact a Trial Team

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International Sites

Danish Center for Particle Therapy, Aarhus, Denmark

Status

Address

Danish Center for Particle Therapy

Aarhus, , 8200

Site Contact

Birgit K Bach

dcpt_kfe@rm.dk

+4529797231

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