DSP-0390 for Brain Tumors

Overseen By Omar H Butt, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must be taking: Antiepileptics, Corticosteroids

Must not be taking: CYP3A4 inhibitors, CYP2D6 inhibitors

Disqualifiers: Multifocal disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You cannot take strong or moderate CYP3A4 inhibitors or inducers, strong CYP2D6 inhibitors, or certain antiepileptic drugs like carbamazepine, phenytoin, and phenobarbital. If you are on antiepileptic medication or corticosteroids, you must be on a stable dose for a specified period before starting the trial.

What data supports the effectiveness of the drug DSP-0390 for brain tumors?

The research highlights that chemotherapy, particularly with drugs like temozolomide, has shown benefits in treating certain types of brain tumors when combined with radiation. This suggests that new drugs like DSP-0390 might also be effective, especially if they can be combined with other treatments to improve outcomes. ^{1 2 3 4 5}

How is the drug DSP-0390 unique for treating brain tumors?

The drug DSP-0390 is unique because it may target specific molecular pathways involved in brain tumor growth, such as the PI3K/Akt pathway, which is often upregulated in these tumors. This approach is different from traditional treatments like chemotherapy and radiotherapy, which are not curative for malignant gliomas. ^{6 7 8 9 10}

What is the purpose of this trial?

This study focuses on determining the pharmacokinetic and pharmacodynamic effect of DSP-0390 in brain and blood from patients with IDH-mutant WHO grade II or III glioma undergoing tumor resection. Tissue will be collected during surgical resection. Blood will be drawn at various time points throughout the 2 weeks of treatment. The hypothesis is that DSP-0390 will accumulate in brain tumor tissue at pharmacologically relevant concentrations, and that alterations in cholesterol metabolism driven by mutant IDH will increase susceptibility to DSP-0390 and lead to tumor cell death.

Research Team

Omar H Butt, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for patients with IDH-mutant WHO grade II or III glioma, a type of brain tumor. Participants must be scheduled for tumor resection surgery and willing to have tissue collected during the procedure. They should also agree to blood draws over two weeks of treatment.

Inclusion Criteria

Ability to understand and sign an IRB approved written informed consent document

Agreement to use adequate contraception by women of childbearing potential and men

I am eligible for surgery to remove a tumor larger than 8 cc.

Exclusion Criteria

Receiving other investigational agents, allergic reactions to compounds similar to DSP-0390

Pregnancy or breastfeeding, HIV with specific criteria, detectable viral load for hepatitis C or evidence of hepatitis B infection

My cancer has spread to multiple areas, including the brain's lining or beyond.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DSP-0390 once daily by mouth for 2 weeks prior to surgical resection, with the final dose administered the morning of surgery. Blood samples are taken at various time points.

2 weeks

Surgical Resection

Tissue is collected during surgical resection to determine the pharmacokinetic and pharmacodynamic effect of DSP-0390 in brain and blood.

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the incidence of adverse events.

4 weeks

Treatment Details

Interventions

• DSP-0390

Trial Overview The study tests DSP-0390's effects in the brain and blood of glioma patients. It aims to see if this drug reaches effective levels in brain tumors and whether it can cause cancer cells to die by targeting cholesterol metabolism changes caused by mutant IDH.

Participant Groups

Group I: DSP-0390 240 mg Experimental Treatment 1 Intervention

The next 10 patients will be assigned to DSP-0390 240 mg once daily by mouth for 2 weeks prior to surgical resection, with the final dose being administered the morning of surgery.

Group II: DSP-0390 120 mg Experimental Treatment 1 Intervention

The first 10 patients will be assigned to DSP-0390 120 mg once daily by mouth for 2 weeks prior to surgical resection, with the final dose being administered the morning of surgery.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Sumitomo Pharmaceuticals America

Industry Sponsor

Trials

5

Recruited

300+

Findings from Research

Malignant gliomas are challenging to treat, with surgery and radiation providing the most significant survival benefits, while chemotherapy offers only modest improvements.

The paper discusses the limited effectiveness of current chemotherapy agents and suggests that future treatments may rely on combination therapies that include both targeted biological compounds and traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of malignant gliomas. Stern, JI., Raizer, JJ.[2007]

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]

In a study of 101 patients with malignant glioma, only 27% were eligible for adjuvant stereotactic radiosurgery, and these eligible patients had significantly longer median survival times (23.4 months) compared to ineligible patients (8.6 months).

The findings suggest a substantial selection bias in uncontrolled trials of stereotactic radiosurgery, indicating that a phase III randomized study may not be necessary as it is unlikely to show positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring bias in uncontrolled brain tumor trials--to randomize or not to randomize? Irish, WD., Macdonald, DR., Cairncross, JG.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of malignant gliomas. [2007]

2. Italy pubmed.ncbi.nlm.nih.gov

Therapeutic strategy for central nervous system tumors: present status, criticism and potential. [2017]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Changing boundaries in the treatment of malignant gliomas. [2012]

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

Measuring bias in uncontrolled brain tumor trials--to randomize or not to randomize? [2019]

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

DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition. [2023]

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

Non-cytotoxic drugs as potential treatments for gliomas. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 2: PI3K/Akt/PTEN, mTOR, SHH/PTCH and angiogenesis. [2021]

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

Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas. [2022]

10. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy of adult glial tumors: new developments and perspectives]. [2008]