The study is designed as an open label, multi-center, Phase 1 study of single agent tinostamustine, used as adjuvant treatment in patients with newly diagnosed GBM who are MGMT unmethylated and have completed concomitant treatment with temozolomide and radiation. Treatment with adjuvant tinostamustine will start within 5 weeks of completion of concomitant temozolomide and radiation. The study is designed to define the MTD by evaluating toxicities during dose escalation. Tinostamustine will be administered on Day 1 of a 21-day treatment cycle.
The total number of treatment cycles is 12 for patients who continue to benefit from treatment without disease progression or intolerable toxicity. Patients will enter a "3+3" design with dose escalation/de-escalation depending on safety from the last treated cohort.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patients must have Grade 4 isocitrate dehydrogenase (IDH) wild type GBM with local pathology confirmed MGMT-promoter unmethylated status.
Exclusion criteria
. A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to first dose of tinostamustine on a stable or decreasing dose of steroids for at least 5 days, is required prior to entrance of a patient onto the study.
. Patients must be registered on the study within 5 weeks of completion of concurrent chemoradiation.
. Patient must be willing and able to provide written informed consent for the study.
. Age ≥18 years on day of signing informed consent.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Dose Limiting toxicity
Timeframe: cycle 1 of treatment. Cycle 1 is 21 days duration with infusion given on day 1
. Prescribed treatment with concomitant temozolomide must be consistent with the EORTC-22981-26981 study (NCT00006353). The dose must be 75 mg/m2 daily for the 6 to 6.5 weeks of radiation therapy. The patient must have completed at least 75% of temozolomide dosing during radiotherapy.
. Confirmed IDH wild type. The presence of an IDH mutation will be exclusionary for study enrolment. IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e., IDH wild type). If a mutation is identified, then the patient will be ineligible.
. Patients must have a performance status of ≥60 on the Karnofsky Performance Scale (KPS).
0. If patient is on steroids, patient must be on a stable or decreasing dose of steroids for at least 5 days at the time of baseline brain MRI.