Quisinostat + Radiotherapy for Glioblastoma

Overseen By Phase 0 Naviagtor

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must be taking: Antiepileptics

Must not be taking: CYP3A4 inhibitors, Torsades de Pointes

Disqualifiers: Pregnancy, Severe infection, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot take strong inhibitors or inducers of CYP3A4 within 2 weeks before starting the study drug, and you must be on a stable anti-epileptic treatment if you have tumor-induced seizures.

What makes the drug Quisinostat unique for treating glioblastoma?

Quisinostat is unique because it is a brain-penetrant histone deacetylase (HDAC) inhibitor that specifically targets class I HDAC isoforms, particularly HDAC1, which is essential in glioblastoma. This specificity and ability to cross the blood-brain barrier make it a promising radiosensitizer, potentially enhancing the effectiveness of radiotherapy in treating glioblastoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Quisinostat when used with radiotherapy for glioblastoma?

Research shows that Quisinostat, a drug that can enter the brain, helps make radiation therapy more effective in treating glioblastoma, a type of brain cancer. In studies with animals, Quisinostat combined with radiation extended survival, suggesting it could be a promising treatment option. ^{1 2 3 6 7}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

This trial is for adults with newly-diagnosed or recurrent Grade 4 IDH-Wildtype Glioblastoma. Participants must have a specific type of brain tumor without certain genetic mutations (IDH-WT). The study has two parts: one for those with new diagnoses and another for those whose cancer has come back.

Inclusion Criteria

Confirmed negative serum pregnancy test before starting study treatment

For females of reproductive potential: use of highly effective contraception

I can swallow pills.

Exclusion Criteria

Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product

Pregnancy or lactation

Known allergic reactions to components of the quisinostat

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants receive quisinostat prior to planned resection; blood, tumor, and CSF samples are collected during surgery

1-2 weeks

1 visit (in-person for surgery)

Expansion Phase 1b

Participants with positive PK response receive therapeutic dosing of quisinostat plus standard-of-care fractionated radiotherapy

2-6 weeks

Multiple visits (in-person for treatment)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Quisinostat

Trial Overview The trial is testing Quisinostat, a drug, combined with standard radiotherapy. It's an early-phase study to see how the body processes the drug and if it's beneficial when added to radiation treatment in patients with this aggressive form of brain cancer.

How Is the Trial Designed?

Group I: Recurrent WHO Grade 4 Glioblastoma IDH-WT Experimental Treatment 1 Intervention

Group II: Newly-Diagnosed WHO Grade 4 Glioblastoma IDH-WT Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Published Research Related to This Trial

Adding nitrosourea-based chemotherapy to radiotherapy has been shown to increase progression-free survival in patients with grade II and III gliomas, although it does not improve overall survival.

Upcoming phase III trials will investigate whether adding temozolomide to radiotherapy can enhance overall survival in grade II/III gliomas, while also assessing cognitive function and quality of life for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. Schiff, D.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Quisinostat is a brain-penetrant radiosensitizer in glioblastoma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Final Report on Clinical Outcomes and Tumor Recurrence Patterns of a Pilot Study Assessing Efficacy of Belinostat (PXD-101) with Chemoradiation for Newly Diagnosed Glioblastoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of concurrent topotecan and radiation on 6-month progression-free survival in the primary treatment of glioblastoma multiforme. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Treatment options for recurrent glioblastoma: pitfalls and future trends. [2009]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. [2017]