ACT001 for Brain Cancer

Recruiting at 17 trial locations

Overseen By Kelsey H Troyer, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Anticancer agents, Investigational drugs

Disqualifiers: Metastatic disease, Uncontrolled infection, Transplant, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

60 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any other anti-cancer agents and investigational drugs. If you are on corticosteroids, you may continue them if the dose is stable or decreasing. Some medications, like certain anticonvulsants and high-dose biotin, are not allowed, and SSRIs should be used with caution. Please discuss your specific medications with the study team to ensure eligibility.

What data supports the effectiveness of the drug ACT001 for brain cancer?

The research highlights the importance of early-phase clinical trials, like phase 0 trials, which help identify promising drugs for brain tumors by studying their effects and how they move through the body. Although specific data on ACT001 is not provided, these trials are crucial for finding effective treatments for brain cancer. ^{1 2 3 4 5}

How is the drug ACT001 different from other treatments for brain cancer?

ACT001 is unique because it can cross the blood-brain barrier and targets glioblastoma by inhibiting the STAT3 pathway, which is involved in tumor growth and immune suppression. This drug also reduces the expression of PD-L1, a protein that helps tumors evade the immune system, making it a novel approach compared to standard treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG.

Research Team

Sara Khan, MD, PhD, FRACP

Principal Investigator

Nationwide Children's Hospital

David S. Ziegler, MD, FRACP

Principal Investigator

Sydney Children's Hospitals Network

Eligibility Criteria

This trial is for patients with specific brain tumors: Diffuse Intrinsic Pontine Gliomas (DIPG) and H3K27-altered High Grade Gliomas (HGG). Detailed inclusion and exclusion criteria are not provided, but typically these would involve age, health status, prior treatments, and tumor characteristics.

Inclusion Criteria

My organs are functioning well.

Life expectancy of ≥ 3 months

My disease can be seen and measured on an MRI.

Exclusion Criteria

Patients who have received a prior solid organ transplantation

I am taking specific medications as outlined in the trial criteria.

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACT001 at 875 mg/m2 orally BID for 28 days per cycle, up to 26 cycles

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Extension

Continuation of treatment beyond 26 cycles may be considered if patients are receiving clinical benefit

Treatment Details

Interventions

• ACT001

Trial Overview The study is testing the safety and effectiveness of a drug called ACT001 in treating DIPG and H3K27-altered HGG. As an open-label Phase II trial, all participants will receive ACT001 without any placebo or comparison treatment.

Participant Groups

Group I: Cohort B Experimental Treatment 1 Intervention

Patients with progressive/refractory/recurrent DIPG or extra-pontine H3K27-altered HGG tumors that have progressed following frontline treatment

Group II: Cohort A Experimental Treatment 1 Intervention

Patients with newly-diagnosed DIPG with typical MRI findings

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Accendatech USA Inc.

Industry Sponsor

Trials

2

Recruited

110+

Findings from Research

Oral targeted agents, including BRAF inhibitors and various receptor inhibitors, show potential in treating brain metastases, but there is a lack of comprehensive data on their effectiveness in this specific area.

Many patients with brain metastases are excluded from clinical trials, leading to a significant gap in research and documentation of the intracranial activity of these therapies, highlighting the need for more focused investigations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Targeted Therapies and Central Nervous System (CNS) Metastases. Gabay, MP., Wirth, SM., Stachnik, JM., et al.[2022]

References

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

Phase 0 Clinical Trial Strategies for the Neurosurgical Oncologist. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Neurooncology clinical trial design for targeted therapies: lessons learned from the North American Brain Tumor Consortium. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Oral Targeted Therapies and Central Nervous System (CNS) Metastases. [2022]

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

Phase 0 and window of opportunity clinical trial design in neuro-oncology: a RANO review. [2021]

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

Development of a core outcome set and identification of patient-reportable outcomes for primary brain tumour trials: protocol for the COBra study. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

ACT001 reduces the expression of PD-L1 by inhibiting the phosphorylation of STAT3 in glioblastoma. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling. [2021]

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

Curcumin changes the polarity of tumor-associated microglia and eliminates glioblastoma. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Blockade of STAT3 Signaling Contributes to Anticancer Effect of 5-Acetyloxy-6,7,8,4'-Tetra-Methoxyflavone, a Tangeretin Derivative, on Human Glioblastoma Multiforme Cells. [2020]

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

The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction in glioma. [2019]