Fimepinostat for Brain Cancer

(PNOC016 Trial)

Not currently recruiting at 22 trial locations

Overseen By Sabine Mueller, MD, PhD, MAS

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Sabine Mueller, MD, PhD

Must not be taking: HDAC inhibitors, PI3K inhibitors

Disqualifiers: Diabetes, HIV, Cardiac arrhythmia, others

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

Compensation: Varies

Number of Visits: 31

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called fimepinostat for certain brain cancers, including newly diagnosed diffuse intrinsic pontine glioma (DIPG), medulloblastoma, and recurrent high-grade glioma. Fimepinostat may inhibit tumor growth by blocking enzymes necessary for cell growth. Participants will take fimepinostat and may undergo surgery to remove or biopsy the tumor. The trial seeks participants who can swallow pills and have one of the specified types of brain cancer. As an Early Phase 1 trial, this research aims to understand how fimepinostat works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids like dexamethasone, you must be on a stable or decreasing dose for at least 7 days before joining. It's best to discuss your specific medications with the study team.

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

Research has shown that fimepinostat is under investigation for its potential to treat brain tumors by blocking enzymes that aid tumor cell growth. Although specific safety data from past studies is not detailed, the trial's early phase indicates that researchers are still assessing how well people tolerate fimepinostat. Early-phase trials typically focus on understanding safety and determining the correct dosage.

Patients in these studies receive close monitoring for any side effects or adverse reactions. If fimepinostat had been approved for another condition, it might suggest some level of established safety, but this information is not provided here. Participants considering joining the trial can expect frequent check-ups to manage any side effects promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fimepinostat is unique because it targets brain cancer differently than current treatments. While most standard treatments for brain cancer involve surgery, radiation, and chemotherapy, fimepinostat works by inhibiting specific enzymes called PI3K and HDAC. This dual inhibition can potentially disrupt the cancer cells' growth and survival pathways more effectively. Researchers are excited because this novel mechanism of action might offer a new avenue for tackling aggressive brain cancers, possibly improving outcomes for patients where other treatments have fallen short.

What evidence suggests that fimepinostat might be an effective treatment for brain cancer?

Research has shown that fimepinostat could be helpful in treating brain tumors. Studies have found that fimepinostat disrupts certain signals in cancer cells, which helps stop tumors from growing. It has shown positive effects, especially when used with radiation therapy, in treating aggressive brain tumors like high-grade gliomas and diffuse intrinsic pontine gliomas. Additionally, combining fimepinostat with another drug, temozolomide, has significantly slowed tumor growth and helped patients live longer compared to using either drug alone. In this trial, participants will receive fimepinostat in combination with tumor resection or biopsy as part of their standard of care. These findings suggest that fimepinostat might be effective in slowing the growth of certain brain tumors. ^{1 2 5 6 7}

Who Is on the Research Team?

Sabine Mueller, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for children and young adults with specific brain tumors (like diffuse intrinsic pontine glioma or high-grade glioma) that are newly diagnosed or have returned. Participants must be able to swallow medication, have recovered from previous cancer treatments, meet certain health criteria including controlled seizures if present, agree to use contraception, and understand the consent form.

Inclusion Criteria

Your corrected QT interval is less than 480 milliseconds.

My kidney and liver functions meet the required levels for my age and gender.

I can swallow pills without needing to crush or chew them.

Exclusion Criteria

You have had an allergic reaction to drugs similar to fimepinostat.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

I have not been treated with HDAC or PI3K inhibitors before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive fimepinostat orally once daily on days -2 to 0, followed by tumor resection or biopsy on day 0

3 days

1 visit (in-person) for surgery or biopsy

Maintenance

Participants receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

12-24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Fimepinostat
• Therapeutic Conventional Surgery

Trial Overview The trial is testing fimepinostat's effectiveness on certain brain tumors by blocking enzymes needed for tumor cell growth. It includes patients who can take the drug orally and have met recovery benchmarks from prior treatments. The study also involves standard care tumor tissue collection.

How Is the Trial Designed?

Group I: Treatment (fimepinostat, tumor resection) Experimental Treatment 2 Interventions

Patients receive fimepinostat by mouth once daily, on Days -2 to 0. Within 2 hours of receiving fimepinostat on Day 0, patients undergo tumor resection or biopsy as part of their standard of care. MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 12 months from the time treatment begins. Should patients continue to derive clinical benefit, and not experience excess toxicity or progression, patients can continue to receive drug for up to 24 months or longer pending discussion with study chairs and study sponsor.

Who Is Running the Clinical Trial?

Sabine Mueller, MD, PhD

Lead Sponsor

Trials

9

Recruited

440+

Cannonball Kids' Cancer Foundation

Collaborator

Trials

6

Recruited

140+

Pediatric Neuro-Oncology Consortium

Collaborator

Pediatric Neuro-Oncology Consortium

Collaborator

Trials

4

Recruited

130+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials

16

Recruited

840+

Cannonball Kids' Cancer Foundation

Collaborator

Trials

4

Recruited

110+

Curis, Inc.

Industry Sponsor

Trials

17

Recruited

1,100+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03893487

NCT03893487 | Fimepinostat in Treating Brain Tumors in ... This trial studies how well fimepinostat works in treating patients with newly diagnosed diffuse intrinsic pontine glioma, or medulloblastoma, or high-grade ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40701845/

Fimepinostat is a dual inhibitor of tumor and angiogenesis ... The combination of fimepinostat and temozolomide significantly inhibited tumor growth and prolonged survival compared to monotherapy or control.

3. aacrjournals.org aacrjournals.org/cancerres/article/84/4/598/734129/Fimepinostat-Impairs-NF-B-and-PI3K-AKT-Signaling

Fimepinostat Impairs NFκB and PI3K/AKT Signaling and ... Fimepinostat showed the antitumor efficacy when it was combined with radiation treatment in pediatric high-grade glioma (HGG) and DIPG (21), and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38095539/

Fimepinostat Impairs NF-κB and PI3K/AKT Signaling and ... Gemcitabine activates p53 and induces apoptosis to elicit antitumor effects in H3.3K27M DIPG, which can be enhanced by blocking NF-κB and PI3K/AKT signaling ...

5. withpower.com withpower.com/trial/early-phase-1-diffuse-intrinsic-pontine-glioma-7-2019-e36da

Fimepinostat for Brain Cancer · Info for Participants This trial studies how well fimepinostat works in treating patients with newly diagnosed diffuse intrinsic pontine glioma, or medulloblastoma, or high-grade ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11394548/

Emerging and Biological Concepts in Pediatric High-Grade ... For tumors located in the supratentorial region, the 5-year overall survival rate is less than 20%, with most patients succumbing to the disease ...

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/glioma

UCSF Glioma Clinical Trials for 2025 — San Francisco Bay Area Patients with glial brain tumors have increasingly improved outcomes, with median survival of 5-15 years.