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 range18 Years
SexALL
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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.
✕. 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.
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