Window of Opportunity Study of DSP-0390 in Gliomas

NCT06636162 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 202412002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on determining the pharmacokinetic and pharmacodynamic effect of DSP-0390 in brain and blood from patients with IDH-mutant 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.

Conditions

Glioma, Malignant; IDH Mutation

Keywords

DSP-0390; IDH-mutant glioma; brain tumor; brain cancer; low grade glioma; high grade glioma

Outcome Measures

Primary Outcomes (2)

• Unbound DSP-0390 concentration in non-enhancing tumor tissue

  Unbound DSP-0390 concentration in non-enhancing tumor tissue will be quantified using tissue removed during resection after treatment.

  At time of surgery following treatment (estimated to be 2 weeks)

• Changes in DSP-0390 concentration in plasma

  Unbound DSP-0390 concentration in plasma will be quantified using blood samples taken throughout treatment.

  From start of treatment through end of treatment (estimated to be 2 weeks)

Secondary Outcomes (23)

• Incidence of treatment emergent adverse events (TEAEs)

  From start of treatment through 30 day follow-up (estimated to be 6 weeks)

• Incidence of grade 3 or higher study drug related adverse events (AEs)

  From start of treatment through 30 day follow-up (estimated to be 6 weeks)

• Lathosterol levels in non-enhancing tumor tissue

  At time of surgery following treatment (estimated to be 2 weeks)

• Changes in lathosterol levels in non-enhancing tumor tissue

  Baseline and at time of surgery following treatment (estimated to be 2 weeks)

• Zymostenol levels in non-enhancing tumor tissue

  At time of surgery following treatment (estimated to be 2 weeks)

Study Arms (2)

Arm A Low Grade Gliomas: DSP-0390 120 mg

EXPERIMENTAL

Patients will be assigned to DSP-0390 120 mg once daily by mouth for approximately 2 weeks and up to 17 days prior to surgical resection, with the final dose being administered the morning of surgery.

Arm B High Grade Gliomas: DSP-0390 180 mg

EXPERIMENTAL

Patients will be assigned to DSP-0390 180 mg once daily by mouth for approximately 1 week prior to surgical resection, with the final dose being administered the morning of surgery.

Interventions

DSP-0390 DRUG

DSP-0390 will be administered orally with preferably 200 mL of water, or approximately one-half cup water. The patient will take DSP-0390 after a minimum of a 6-hour fast and will fast for 1 hour after taking the dose.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have either newly diagnosed and suspected glioma per radiographic features, or radiographic recurrence of a histologically confirmed IDH-mutant glioma with the following grade requirements:
• ARM A: suspected lower grade glioma, or histologically confirmed grade II IDH-mutant glioma OR
• ARM B: suspected high grade glioma, or histologically confirmed grade III or IV glioma.
• Patient must be a candidate for surgical resection
• At least 18 years of age.
• Karnofsky ≥ 70%
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm (patient may not use G-CSF or GM-CSF to achieve this ANC level)
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9 g/dL (patient may not receive transfusion or use erythropoietin to obtain this Hgb level)
• Total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with known Gilbert's syndrome)
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• International normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), or activated partial thromboplastin time (aPTT) ≤1.5 x ULN. The use of anticoagulants is permitted as long as the PT/(a)PTT is within therapeutic limits (according to the local institution standard) and the patient has been on a stable anticoagulant regimen for at least 2 weeks prior to Day 1.
• Creatinine Clearance of ≥40 mL/min per Cockroft-Gault formula or by a 24 hour urine.
• If a patient is using an antiepileptic medication, the patient is on a stable dose and without seizures for 14 days prior to Day 1. The antiepileptic medication used must not fall under any prohibited therapy category as defined in the protocol.

You may not qualify if:

• Patient has had prior therapy with bevacizumab or other anti-vascular endothelial growth factor (VEGF) treatments within 3 months prior to Day 1.
• Patient has multifocal disease, leptomeningeal metastasis, or extracranial metastasis.
• Patient has a clinically significant abnormal ECG, including those where QT prolongation is determined by the Fridericia formula (QTcF \>450 msec for males and \>470 msec for females); and/or the patient has a history of Torsade de Pointes.
• Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other condition that may limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Patient is known to have active Crohn's or other inflammatory bowel disease.
• A history of other malignancy for which all treatment was completed at least 2 years before Day 1 and the patient has no evidence of disease. Exceptions include non-melanoma skin cancer, cervical carcinoma in situ, and superficial bladder cancer that has been removed or curatively treated.
• On active treatment for other, unrelated malignancy or currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DSP-0390.
• Patient has taken concurrent use of prohibited medications: carbamazepine, phenytoin, phenobarbital, and other strong or moderate CYP3A4 inhibitors or inducers, and strong CYP2D6 inhibitors within 1 week or 5 half-lives (whichever is greater) prior to Day 1 or expects to use them during the study. Note both oral and IV ondansetron at doses ≤ 8mg q6 hours are permitted.
• The presence of any active retinal abnormality determined by screening ophthalmologic examination.
• Patient has significant cardiovascular disease, including New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction, unstable angina, pectoris, clinically significant cardiac arrhythmias, or stroke in the preceding 6 months prior to Day 1.
• Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements, disorders associated with significant immunocompromised state, or ongoing or active infection.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of DSP-0390.
• Patient has a known detectable viral load for hepatitis C, or evidence of a hepatitis B surface antigen.
• Patient has had a major non-neurologic surgical procedure, surgical resection, open biopsy, or significant traumatic injury within 4 weeks prior to Day 1 or anticipates needing a major surgical procedure during the course of the study.

Sponsors & Collaborators

• The Foundation for Barnes-Jewish Hospital: collaborator
• Washington University School of Medicine: lead
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Omar H Butt, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

314-747-4241; omarhbutt@wustl.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 10, 2024
• Study Start: April 3, 2025
• Primary Completion (Estimated): April 17, 2027
• Study Completion (Estimated): May 17, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (1)