A Phase 0/1b 'Trigger' Clinical Trial With an Expansion Phase of Quisinostat Plus Fractionated Radiotherapy in Newly-diagnosed and Recurrent Grade 4 IDH-WT Glioblastomas
This is an open-label, multi-center Phase 0/1b study that will enroll up to 18 participants with recurrent WHO grade 4 glioblastoma (rGBM) IDH-wildtype (IDH-WT), Arm A, and 12 participants with presumed newly-diagnosed WHO grade 4 glioblastoma (nGBM) IDH-WT, Arm B. The trial will be composed of a Phase 0 component (subdivided into Arms A and B), and an Expansion Phase 1b. Patients with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component of the study will graduate to an Expansion Phase that combines therapeutic dosing of quisinostat plus standard-of-care fractionated radiotherapy (RT).
• For Arm A: Participants who have had a prior resection of diagnosed glioblastoma, IDH wildtype (2021 WHO grade 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy. Participants will also need to have radiation planned as part of the post-surgical treatment plan; OR, for Arm B only: Participants undergoing resection for a suspected newly diagnosed WHO Grade 4 glioblastoma, IDH wildtype. Participants will also need to have radiation planned as part of the post-surgical treatment plan.
• Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
• Provision of signed and dated, written informed consent (personally or by the legally authorized representative, if applicable) prior to any study specific procedures, sampling and analyses.
• Age ≥18 at time of consent
• Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Ability to swallow oral medications.
• Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• Participants with tumor-induced seizures must be well-controlled on a stable anti-epileptic treatment.
• Participants must be willing to receive prophylaxis with levetiracetam for the duration of study drug administration (or alternative anti-epileptic if agreed with Medical Monitor).
• Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
• For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation until the end of treatment administration and for 16 weeks after the last dose of study drug.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner until the end of treatment administration and for 16 weeks after the last dose of study drug.
• Agreement to adhere to Lifestyle Considerations throughout study duration.