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 trial explores a new treatment for glioblastoma, an aggressive brain cancer. It combines a drug called quisinostat with standard radiation therapy to determine if it can better assist those with either recurrent or newly diagnosed glioblastoma. The trial includes two groups: one for individuals with recurrent glioblastoma and another for those newly diagnosed. It seeks participants with glioblastoma who have planned radiation treatment as part of their care. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Quisinostat, a drug that can enhance the effects of radiation therapy for glioblastoma (a type of brain cancer), is generally well-tolerated by patients. In earlier studies, participants managed the combination of Quisinostat and radiation throughout the treatment. No major side effects occurred at certain doses. Further studies will continue to monitor safety and patient tolerance with radiation. This suggests that Quisinostat appears safe when used with radiation, but ongoing research will provide more detailed information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Quisinostat is unique because it targets glioblastomas by inhibiting histone deacetylases (HDACs), a different approach compared to standard treatments like temozolomide or radiation alone. This mechanism may help in preventing tumor cell growth and resistance, which is a big challenge with current therapies. Researchers are excited about Quisinostat because it could enhance the effectiveness of radiotherapy, potentially leading to better outcomes for patients with glioblastoma.

What evidence suggests that quisinostat plus radiotherapy could be an effective treatment for glioblastoma?

Research shows that Quisinostat can enhance the effectiveness of radiation treatment against glioblastoma, a type of brain cancer. This trial will evaluate Quisinostat combined with radiotherapy for two groups: those with recurrent WHO Grade 4 Glioblastoma IDH-WT and those newly diagnosed with the same condition. Quisinostat can penetrate the brain where the tumor resides. Studies have found that Quisinostat helps shrink tumors and targets glioma cells, the cancerous cells in glioblastoma. Combining it with radiotherapy shows promise in reducing tumor size. Although research remains in the early stages, Quisinostat is believed to increase cancer cells' sensitivity to radiation, potentially improving treatment effectiveness. ^{1 2 3 4 6}

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06824662

Study Details | NCT06824662 | Phase 0 With Expansion ... 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 ...

2. insight.jci.org insight.jci.org/articles/view/167081

Quisinostat is a brain-penetrant radiosensitizer in ... These results suggest that 10 mg/kg dosing of QST is effective in reducing tumor burden and induces the intended PD effects in glioma cells, and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10721329/

Quisinostat is a brain-penetrant radiosensitizer in glioblastoma Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors.

4. withpower.com withpower.com/trial/early-phase-1-glioblastoma-4-2025-373bf

Quisinostat + 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.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06824662?term=JNJ%2026481585&rank=4

Phase 0 With Expansion Phase Clinical Trial of Quisinostat ... 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 ...

6. ivybraintumorcenter.org ivybraintumorcenter.org/brain-tumor-clinical-trials/current-trials/quisinostat-for-glioblastoma/

QUISINOSTAT FOR GLIOBLASTOMA The expansion phase will examine progression-free survival and monitor safety and tolerability of Quisinostat in combination with radiation.